Aims. The aim of this study was to develop a core outcome set of what to measure in all future clinical research on hand fractures and
To explore the synovial expression of mucin 1 (MUC1) and its role in rheumatoid arthritis (RA), as well as the possible downstream mechanisms. Patients with qualified synovium samples were recruited from a RA cohort. Synovium from patients diagnosed as non-inflammatory orthopaedic arthropathies was obtained as control. The expression and localization of MUC1 in synovium and fibroblast-like synoviocytes were assessed by immunohistochemistry and immunofluorescence. Small interfering RNA and MUC1 inhibitor GO-203 were adopted for inhibition of MUC1. Lysophosphatidic acid (LPA) was used as an activator of Rho-associated pathway. Expression of inflammatory cytokines, cell migration, and invasion were evaluated using quantitative real-time polymerase chain reaction (PCR) and Transwell chamber assay.Aims
Methods
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Objectives. Metabolic syndrome and low-grade systemic inflammation are associated with knee osteoarthritis (OA), but the relationships between these factors and OA in other synovial joints are unclear. The aim of this study was to determine if a high-fat/high-sucrose (HFS) diet results in OA-like
Post-traumatic osteoarthritis (PTOA) is a subset of osteoarthritis, which occurs secondary to traumatic
Senescent chondrocyte and subchondral osteoclast overburden aggravate inflammatory cytokine and pro-catabolic proteinase overproduction, accelerating extracellular matrix degradation and pain during osteoarthritis (OA). Fibronectin type III domain containing 5 (FNDC5) is found to promote tissue homeostasis and alleviate inflammation. This study aimed to characterize what role Fndc5 may play in chondrocyte aging and OA development. Serum and macroscopically healthy and osteoarthritic cartilage were biopsied from patients with knee OA who received total knee replacement. Murine chondrocytes were transfected with Fndc5 RNAi or cDNA. Mice overexpressing Fndc5 (Fndc5Tg) were operated to have destabilized medial meniscus mediated (DMM)
The August 2023 Children’s orthopaedics Roundup. 360. looks at: DDH: What can patients expect after open reduction?; Femoral head deformity associated with hip displacement in non-ambulatory cerebral palsy; Bony hip reconstruction for displaced hips in patients with cerebral palsy: is postoperative immobilization indicated?; Opioid re-prescriptions after ACL reconstruction in adolescents are associated with subsequent opioid use disorder; Normative femoral and tibial lengths in a modern population of USA children; Retrospective analysis of associated anomalies in 636 patients with operatively treated congenital scoliosis; Radiological hip shape and patient-reported outcome measures in healed Perthes’ disease; Significantly displaced adolescent posterior sternoclavicular
Aims. Insufficient treatment response in rheumatoid arthritis (RA) patients requires novel treatment strategies to halt disease progression. The potential benefit of combination of cytokine-inhibitors in RA is still unclear and needs further investigation. To explore the impact of combined deficiency of two major cytokines, namely interleukin (IL)-1 and IL-6, in this study double deficient mice for IL-1αβ and IL-6 were investigated in different tumour necrosis factor (TNF)-driven inflammatory bone disorders, namely peripheral arthritis and sacroiliitis, as well as systemic bone loss. Methods. Disease course, histopathological features of arthritis, and micro-CT (µCT) bone analysis of local and systemic bone loss were assessed in 15-week-old IL1-/-IL6-/-hTNFtg in comparison to IL1-/-hTNFtg, IL6-/-hTNFtg, and hTNFtg mice. µCT bone analysis of single deficient and wild-type mice was also performed. Results. Combined deficiency of IL-1/IL-6 markedly ameliorated TNF-mediated arthritis and bilateral sacroiliitis, but without additive benefits compared to single IL-1 deficiency. This finding confirms the important role of IL-1 and the marginal role of IL-6 in TNF-driven pathways of local
Development of osteoarthritis (OA) correlates with epigenetic alteration in chondrocytes. H3K27me3 demethylase UTX is known to regulate tissue homeostasis, but its role in the homeostasis of articulating joint tissue is poorly understood. Forced UTX expression upregulated H3K27me3 enrichment at the Sox9 promoter region to inhibit key extracellular matrix (ECM) molecules, like e.g. type II collagen, aggrecan, and glycosaminoglycans in articular chondrocytes. Utx loss in vitro altered the H3K27me3-binding epigenomic landscape, which contributes to mitochondrial activity, cellular senescence, and cartilage development. Functional target genes of Utx comprise insulin-like growth factor 2 (Igf2) and polycomb repressive complex 2 (PRC2) core components Eed and Suz12. Specifically, Utx deletion promoted Tfam transcription, mitochondrial respiration, ATP production and Igf2 transcription, but inhibited Eed and Suz12 expression. Igf2 inhibition or forced Eed or Suz12 expression increased H3K27 trimethylation and H3K27me3 enrichment at the Sox9 promoter, compromising Utx loss-induced ECM overproduction. Overexpression of Utx in murine knee joints aggravated OA development, including articular cartilage damage, synovitis, osteophyte formation, and subchondral bone loss. Transgenic mice with a chondrocytespecific Utx knockout develop thicker articular cartilage as compared to wild-type controls and show fewer gonarthrotic symptoms during destabilized medial meniscus- and collagenase-induced
Glenohumeral
Osteoarthritis (OA) is the leading cause of pain and disability worldwide and is characterized by the degenerative changes of articular cartilage. Joint loading is required for cartilage maintenance; however, hyper-physiologic loading is a risk factor for OA. Mechanosensitive ion channels Piezo1 and Piezo2 synergistically transduce hyper-physiologic compression of chondrocytes, leading to chondrocyte death and onset of OA. This injury response is inhibited by Piezo channel loss of function, however the mechanistic role of Piezo channels in vivo is unknown. We examined the hypothesis that deletion of Piezo in chondrocytes will protect mice from
Abstract. Objectives. The syndesmosis joint, located between the tibia and fibula, is critical to maintaining the stability and function of the ankle
Hip Osteoarthritis (HOA) is the most common joint disorder and a major cause of disability in the adult population, leading to total hip replacement (THR). Recently, evidence has mounted for a prominent etiologic role of femoroacetabular impingement (FAI) in the development of early OA in the non-dysplastic hip. FAI is a pathological mechanical process, caused by abnormalities of the acetabulum and/or femur leading to damage the soft tissue structures. FAI can determine chondro-labral damage and groin pain in young adults and can accelerate HOA progression in middle-aged adults. The aim of the study was to determine if the presence of calcium crystal in synovial fluid (SF) at the time of FAI surgery affects the clinical outcomes to be used as diagnostic and predictive biomarker. 49 patients with FAI undergoing arthroscopy were enrolled after providing informed consent; 37 SFs were collected by arthrocentesis at the time of surgery and 35 analyzed (66% males), median age 35 years with standard deviation (SD) 9.7 and body mass index (BMI) 23.4 kg/m. 2. ; e SD 3. At the time of surgery, chondral pathology using the Outerbridge score, labral pathology and macroscopic synovial pathology based on direct arthroscopic visualization were evaluated. Physical examination and clinical assessment using the Hip disability & Osteoarthritis Outcome Score (HOOS) were performed at the time of surgery and at 6 months of follow up. As positive controls of OA signs, SF samples were also collected from cohort of 15 patients with HOA undergoing THR and 12 were analysed. 45% FAI patients showed CAM deformity; 88% presented labral lesion or instability and 68% radiographic labral calcification. 4 patients out of 35 showed moderate radiographic signs of OA (Kellegren-Lawrence score = 3). Pre-operative HOOS median value was 61.3% (68.10-40.03) with interquartile range (IQR) of 75-25% and post-operative HOOS median value 90% with IQR 93.8-80.60. In both FAI and OA patients the calcium crystal level in SFs negatively correlated with glycosaminoglycan (component of the extracellular matrix) released, which is a marker of cartilage damage (Spearman rho=-0.601, p<0.001). In FAI patients a worst articular function after surgery, measured with the HOOS questionnaire, was associated with both acetabular and femoral chondropathy and degenerative labral lesion. Moreover, radiographic labral calcification was also significantly associated with pain, worst articular function and labral lesion. Calcium crystal level in SFs was associated with labral lesions and OA signs. We concluded that the levels of calcium crystals in FAI patients are correlated with
Although remnant-preserved ACL reconstruction (ACLR) restores knee joint stability and dampens the problem of acute ACL rupture-induced knee pain, an increasing number of patients still develop post-traumatic osteoarthritis (PTOA) after 10 to 15 years of ACLR. We previously found that remnant-preserved ACLR with concomitant medial and lateral meniscus repair may not prevent cartilage degeneration and weaken muscle strength, while the clinical features of PTOA are not clear. We hypothesized that remnant-preserved ACLR with concomitant medial and lateral meniscus tears is related to early cartilage damage, worse function recovery, patient-reported outcomes (PROs) and delayed duration to return to sports. The aim is to evaluate the remnant-preserved ACLR with complicated meniscal injuries in predicting which patients are at higher risk of osteoarthritic changes, worse function and limited activities after ACLR for 12 months. Human ethical issue was approved by a committee from Xi'an Jiaotong University. 26 young and active patients (24 male, 2 female) with ACL injuries (Sherman type I and II) with concomitant medial and lateral meniscus within 2 months were included from January 2014 to March 2022. The average age of the ACLR+ meniscus repair was 26.77±1.52 (8 right, 5 left) and isolated ACLR control was 31.92±2.61 years old (7 left, 6 right). Remnant-preserved ACLR with a 5- to 6-strand hamstring tendon graft was operated on by the same sports medicine specialists. MRI CUBE-T. 2. scanning with 48 channels was conducted by a professional radiologist. The volume of the ACL graft was created through 3 dimensional MRI model (Mimics 19, Ann Arbor). Anterior Cruciate Ligament OsteoArthritis Score (ACLOAS) was applied to score visible cartilage damage. IKDC 2000 score and VAS were assessed by two blinded researchers. Results were presented as mean± SEM of each group. The cross-sectional area and 3D volume of the ACL graft were greater in the remnant-preserved ACLR+meniscus group compared with isolated ACLR (p=0.01). It showed that ACLR+ meniscus group had early signs of
Abstract. INTRODUCTION. The mechanisms underlying abnormal joint mechanics are poorly understood despite it being a major risk factor for developing osteoarthritis. Glutamate signalling has been implicated in osteoarthritic bone changes and AMPA/kainate glutamate receptor (GluR) antagonists alleviate degeneration in rodent models of osteoarthritis. We investigated whether glutamate signalling molecules are mechanically regulated in a human, cell-based 3D model of bone. METHODS. Human Y201 MSC cells embedded in 3D type I collagen gels (0.05 × 106 cell/gel) differentiated to osteocytes were mechanically loaded in silicone plates (5000 µstrain, 10Hz, 3000 cycles) or not loaded (n=5/group). RNA extracted 1-hr post load was quantified by RTqPCR and RNAseq whole transcriptome analysis (NovaSeq S1 flow cell 2 × 100bp PE reads). Differentially expressed GluRs and glutamate transporters (GluTs) were identified using DEseq2 analysis on normalised count data. Genes were considered differentially expressed if >2 fold change and FDR p<0.05. RESULTS. Cells expressed mature osteocyte markers (E11, sclerostin, DMP-1). DEseq2 analysis, revealed 981 mechanically regulated genes. Mechanical loading upregulated kainate GluRs, GRIK2 (1.6 fold, p=0.024) and GRIK5 (4.2 fold, p=0.045); the NMDA GluR GRIN3B (3.25 fold, p=0.047) and the GluT SLC1A1 (3 fold, p=0.037). Conversely, AMPA GRIA3, NMDA GluRs GRIN2A&C, and the GluT SLC1A2 were down regulated by 50–60%, although not significant. Kainate GRIK3&4; AMPA GRIA2, NMDA GRIN1, and GluTs SLC1A6&A7 were not expressed in control or loaded osteocytes, whereas GluRs (GRIK1, GRIA1&4, GRIN2B&2D&3A) and GluT SLC1A3 were expressed but not regulated by mechanical loading. DISCUSSION. Mechanical loading of human osteocytes in 3D revealed that they regulated expression of glutamate receptors and transporters. This is consistent with our observation that mechanical perturbation after
Rheumatoid arthritis is the most common inflammatory disease of the joints affecting about 0.5% of adults, women more often than men with a peak age of onset of 35–45 years. It is usually progressive affecting further joints and the destructive disease process causes irreversible bony erosions and the joints become structurally deformed, with long-term pain and disability. It has an early and significant impact on the person’s ability to work and socio-economic status with work capacity restricted in a third within a year and within 3 years almost half 40 may be registered work disabled. The aims of management of rheumatoid arthritis are to reduce pain an inflammation; reduce disability; prevent
Aims. A pilon fracture is a severe ankle
Aim. Septic arthritis (SA) is considered a medical emergency. The most common etiological agents are glucose consuming bacteria, so we evaluated the clinical utility of synovial fluid (SF) glucose levels and other biochemical parameters for supporting the diagnosis of the disease and their association with a positive bacteria culture and joint destruction. Methods. Adult patients with SA diagnose were enrolled prospectively between July 2018 and October 2019. As control group, adults with knee osteoarthritis, meniscus and/or knee ligaments lesions were enrolled. SF samples were obtained from the joints by arthrocentesis/arthrotomy. Microbiological analyses of SF were performed using Brucella broth blood culture flasks, samples were incubated at 37°C with 5% CO. 2. for 24 hours. Gram stain, chocolate and blood agar were used for the identification and growth of the bacteria. SF glucose levels, pH and leukocyte esterase were measured as biochemical parameters using a glucometer and colorimetric test strips. The Outerbridge classification was used for grading the osteochondral injury. Furthermore, blood samples were collected from patients and control subjects for determining glucose levels. Results. We included 8 subjects with knee ligaments lesions, 6 with meniscus lesions and 5 with osteoarthritis as control group, as well as 20 patients with SA diagnose. The mean age of the patients was 57.8 years with a 65% of male predominance. The most common affected joint was the knee (85%). SF culture was positive in 60% of the cases and the most common etiological agent was Staphylococcus aureus (58.3%). SF glucose levels from patients were lower than the controls (P=0.0018) and showed the lowest concentration in patients with a positive culture (P=0.0004). There was also a difference between blood and SF glucose concentration from the positive culture patients (P<0.0001). Leucocyte esterase presented the highest values in positive culture patients (P=<0.0001) and a more acidic pH was found compared to the control group (P<0.0001). Regarding the osteochondral injury, the lowest concentrations of SF glucose were found in patients with a higher grade in the classification (P = 0.0046). Conclusions. SF glucose and leukocyte esterase concentrations might be a quick and cheap useful parameter for the physician for distinguishing between bacterial infection and not infected joint. In addition, the lowest SF glucose levels might give information about the
Osteoarthritis (OA) is a disease that affects both bone and cartilage. Typically, this disease leads to cartilage degradation and subchondral bone sclerosis but the link between the two is unknown. Also, while OA was traditionally thought of as non-inflammatory condition, it now seems that low levels of inflammation may be involved in the link between these responses. This is particularly relevant in the case of Post-Traumatic OA (PTOA), where an initial phase of synovial inflammation occurs after injury. The inflammatory mediator interleukin 1 beta (IL-1B) is central to this response and contributes to cartilage degradation. However, whether there is a secondary effect of this mediator on subchondral bone, via bone-cartilage crosstalk, is not known. To address this question, we developed a novel patellar explant model, to study bone cartilage crosstalk which may be more suitable than commonly used femoral head explants. The specific aim of this study was to validate this novel patellar explant model by using IL-1B to stimulate the inflammatory response after
Purpose. Operative treatment of Lisfranc
Aims. Arthrofibrosis is a relatively common complication after
Aim of study Setting an investigation and therapeutical algorythm in paediatric patients with a distal tibiofibular
Introduction. Septic arthritis of the native knee often results in irreversible
Introduction and Aims: Late degeneration of the ACL injured knee may be in part due to repeat injury, but also due to aberrant kinematics altering the wear pattern at the chondral surface. The aim of this study was to use tibio-femoral contact mapping by MRI to examine kinematic changes due to chronic ACL deficiency. Method: Twenty subjects with a recent unilateral ACL deficiency (mean 13 months since injury) and 23 subjects with a chronic ACL deficiency (mean 18 years since injury) were recruited. Passive ligament laxity was quantified using a KT1000® device. Subjects performed a closed-chain leg press, relaxed and against a 15 kg weight. MRI recorded the tibio-femoral contact position at 15-degree intervals from zero to 90 degrees of knee flexion. Tibio-femoral contact points were measured at each position. Damage to the knee was recorded for all subjects by MRI, and at arthroscopy. Results: The tibio-femoral contact pattern of the ACL injured knee was different from the healthy contralateral knee (p = 0.001). The contact pattern of the recently injured knees was different to the chronic ACL deficient knees (p = 0.034). In the recently injured knees the lateral compartment of the knee showed a posterior pattern of femoral contact, and in the chronic ACL deficient knees the medial compartment showed a posterior femoral contact pattern, particularly at zero and 15 degrees of knee flexion (p <
0.01), with the femur two millimetres (mean, SD 3.2mm) posterior on the tibial plateau. There was no difference in passive laxity between the recent and chronic injured knees (side-to-side difference: 5.8mm±2.4 for the recently injured knees, and 4.6±2.8mm for the chronic ACL-deficient knees). Nine of 20 recently injured knees had associated
Osteoarthritis (OA) is a multifactorial debilitating disease that affects over four million Canadians. Although the mechanism(s) of OA onset is unclear, the biological outcome is cartilage degradation. Cartilage degradation is typified by the progressive loss of extracellular matrix components - aggrecan and type II collagen (Col II) – partly due to the up-regulation of catabolic enzymes - aggrecanases a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS-) 4 and 5 and matrix metalloproteinases (MMPs). There is currently no treatment that will prevent or repair
Post-traumatic arthritis is a frequent consequence of articular fracture. The mechanisms leading to its development after such injuries have not been clearly delineated. A potential contributing factor is decreased viability of the articular chondrocytes. The object of this study was to characterise the regional variation in the viability of chondrocytes following joint trauma. A total of 29 osteochondral fragments from traumatic injuries to joints that could not be used in articular reconstruction were analysed for cell viability using the fluorescence live/dead assay and for apoptosis employing the TUNEL assay, and compared with cadaver control fragments. Chondrocyte death and apoptosis were significantly greater along the edge of the fracture and in the superficial zone of the osteochondral fragments. The middle and deep zones demonstrated significantly higher viability of the chondrocytes. These findings indicate the presence of both necrotic and apoptotic chondrocytes after
The paramount importance of synovial fluid in lubrication and protection of articular joints has long been recognized. Synovial fluid, a dialysate of plasma, forms an interface with both the synovium and cartilage and plays a crucial role in joint lubrication and bearing functions. In an osteoarthritic
Osteoarthritis (OA) is the most common musculoskeletal disease in the EU and is characterized by cartilage degeneration, pain and restricted movement. Post-Traumatic OA (PTOA) is a specific disease subset that occurs subsequent to traumatic injury, such as ACL rupture and makes up 12% of the overall disease burden. Our current understanding PTOA is that initial injury affects multiple tissues, and many/all contribute to overall ‘joint failure.’ MRI scans show that subchondral bone marrow lesions (BMLs) are present in 80% of ACL rupture cases in the immediate aftermath of
In least 12% of patients with symptomatic OA, the cause is
Onset and progression of osteoarthritis (OA) is affected by a plethora of factors, including
Juvenile idiopathic arthritis (JIA) is a chronic disease of childhood; it causes
Introduction Late degeneration of the ACL injured knee may be in part due to repeat injury, but also due to aberrant kinematics altering the wear pattern at the chondral surface. The aim of this study was to use tibio-femoral contact mapping by MRI to examine kinematic changes due to chronic ACL deficiency. Methods Twenty-three subjects with a history of chronic ACL deficiency (mean 18 years since injury) performed a closed chain leg press, relaxed and against a 15 kilogram weight. MRI recorded the tibio-femoral contact position at 15° intervals from 0° to 90° of knee flexion. Intra-articular pathology was assessed for all subjects by MRI, and at arthroscopy for 10 subjects. Results The tibio-femoral contact pattern of the ACL injured knee differed from the healthy contralateral knee (p=0.003). This difference was greatest in the medial compartment, particularly at 0° and 15° of knee flexion (p<
0.01), with the femur two millimetres (mean, SD 3.2 mm) posterior on the tibial plateau. Damage to the chondral surface was seen in the medial compartment in 16 subjects and lateral compartment in 12; medial meniscus damage was present in 16 subjects and lateral meniscus in 15. Chondral surface damage correlated with the difference in the tibio-femoral contact pattern between the healthy and injured knee in the medial compartment of the knee.
Ligaments, menisci and joint capsules were obtained from experimental knees with post-traumatic joint contractures and their unoperated contralateral controls in 6 rabbits. Relative mRNA expression was altered for six of seven matrix molecules, growth factors and _-SMA (myofibroblast marker) in the joint capsule, four of seven molecules in the ACL, and two of seven molecules in the MCL and medial meniscus. The joint capsule had the most molecules with altered expression corresponding to it’s acknowledged key role in joint contracture development. Changes in molecular expression of several joint structures in post-traumatic contractures is similar to changes seen following ligament injury. To evaluate alteration of mRNA expression in ligaments, meniscus and joint capsules in post-traumatic contractures. mRNA expression was altered most frequently in the joint capsule. The mRNA expression alterations in the joint capsule reflect it’s significant contribution to contractures. The right knee had a stable intraarticular fracture coupled with Kirschner wire immobilization while the left knee was not surgically manipulated. The rabbits (n=6) were sacrificed two weeks later, and the ACL, MCL, posterior joint capsule and medial meniscus were obtained from both knees. Semiquantitative RT-PCR was used to evaluate relative mRNA expression of selected matrix molecules, growth factors and _-smooth muscle actin (_-SMA), a myofibroblast marker. Glyc-eraldehyde-3-phosphate dehydrogenase, a housekeeping gene, served as a normalization. Optical density measures of the gels were used for analysis. Statistical comparisons were made with a paired t-test. Statistical significance was p<
0.05. Relative mRNA expression was altered for six of seven molecules in the joint capsule, four of seven molecules in the ACL, and two of seven molecules for the MCL and meniscus. For the joint capsule, relative mRNA expression in the contracture capsule was 2-4x greater than the expression in the control capsules, except for TIMP one where the expression in the contracture capsule was 1/3 of the control capsules. As has been noted with other
Purpose: The presence of hemarthrosis during
Osteoarthritis (OA) is associated with biochemical and mechanical processes that release different wear particles into the synovial fluid. Unfortunately, symptoms such as pain, swelling and limited range of motion often do not correlate with the level of OA as observed by X-ray. In addition, the mechanisms of OA and the processes involved are still not clearly understood. Therefore, there is much interest in developing new diagnostic techniques that would provide means to both sensitive, objective determination of
Adult male C57Bl/6 mice (n = 75) were randomized into three groups to receive 1.0 to 1.4 × 107 colony-forming units (CFUs)/ml of 8325-4, DU1090, or saline into the right stifle joint. Chondrocyte death was assessed by confocal microscopy. Histological changes to inoculated joints were graded for inflammatory responses along with gait, weight changes, and limb swelling.Aims
Methods
Post-traumatic osteoarthritis (PTOA) is a subset of osteoarthritis (OA). The gut microbiome is shown to be involved in OA. However, the effect of exercise on gut microbiome in PTOA remains elusive. A total of 18 eight-week Sprague-Dawley rats were assigned into three groups: Sham/sedentary (Sham/Sed), PTOA/sedentary (PTOA/Sed), and PTOA/treadmill-walking (PTOA/TW). PTOA model was induced by transection of the anterior cruciate ligament (ACLT) and the destabilization of the medial meniscus (DMM). Treadmill-walking (15 m/min, 30 min/d, five days/week for eight weeks) was employed in the PTOA/TW group. The response of cartilage, subchondral bone, serology, and gut microbiome and their correlations were assessed.Aims
Methods
Background. Epigenetic regulation of gene transcription affects metabolism of chondrocytes and synovial fibroblasts and is associated with the prevalence of osteoarthritis (OA) of knees. Histone lysine demethylase (KDMs) reportedly modulates tissue homeostasis and deterioration. This study investigated whether KMD6a inhibitor treatment affected the
The April 2023 Research Roundup360 looks at: Ear protection for orthopaedic surgeons?; Has arthroscopic meniscectomy use changed in response to the evidence?; Time to positivity of cultures obtained for periprosthetic joint infection; Bisphosphonates for post-COVID-19 osteonecrosis of the femoral head; Missing missed fractures: is AI the answer?; Congenital insensitivity to pain and correction of the knee; YouTube and paediatric elbow injuries.
The aim of this study was to determine the consensus best practice approach for the investigation and management of children (aged 0 to 15 years) in the UK with musculoskeletal infection (including septic arthritis, osteomyelitis, pyomyositis, tenosynovitis, fasciitis, and discitis). This consensus can then be used to ensure consistent, safe care for children in UK hospitals and those elsewhere with similar healthcare systems. A Delphi approach was used to determine consensus in three core aspects of care: 1) assessment, investigation, and diagnosis; 2) treatment; and 3) service, pathways, and networks. A steering group of paediatric orthopaedic surgeons created statements which were then evaluated through a two-round Delphi survey sent to all members of the British Society for Children’s Orthopaedic Surgery (BSCOS). Statements were only included (‘consensus in’) in the final agreed consensus if at least 75% of respondents scored the statement as critical for inclusion. Statements were discarded (‘consensus out’) if at least 75% of respondents scored them as not important for inclusion. Reporting these results followed the Appraisal Guidelines for Research and Evaluation.Aims
Methods
The February 2024 Trauma Roundup360 looks at: Posterior malleolus fractures: what about medium-sized fragments?; Acute or delayed total hip arthroplasty after acetabular fracture fixation?; Intrawound antibiotics reduce the risk of deep infections in fracture fixation; Does the VANCO trial represent real world patients?; Can a restrictive transfusion protocol be effective beyond initial resuscitation?; What risk factors result in avascular necrosis of the talus?; Pre-existing anxiety and mood disorders have a role to play in complex regional pain syndrome; Three- and four-part proximal humeral fractures at ten years.
For the increasing number of working-age patients undergoing total hip or total knee arthroplasty (THA/TKA), return to work (RTW) after surgery is crucial. We investigated the association between occupational class and time to RTW after THA or TKA. Data from the prospective multicentre Longitudinal Leiden Orthopaedics Outcomes of Osteoarthritis Study were used. Questionnaires were completed preoperatively and six and 12 months postoperatively. Time to RTW was defined as days from surgery until RTW (full or partial). Occupational class was preoperatively assessed and categorized into four categories according to the International Standard Classification of Occupations 2008 (blue-/white-collar, high-/low-skilled). Cox regression analyses were conducted separately for THA and TKA patients. Low-skilled blue-collar work was used as the reference category.Aims
Methods
Pellino1 (Peli1) has been reported to regulate various inflammatory diseases. This study aims to explore the role of Peli1 in the occurrence and development of osteoarthritis (OA), so as to find new targets for the treatment of OA. After inhibiting Peli1 expression in chondrocytes with small interfering RNA (siRNA), interleukin (IL)-1β was used to simulate inflammation, and OA-related indicators such as synthesis, decomposition, inflammation, and apoptosis were detected. Toll-like receptor (TLR) and nuclear factor-kappa B (NF-κB) signalling pathway were detected. After inhibiting the expression of Peli1 in macrophages Raw 264.7 with siRNA and intervening with lipopolysaccharide (LPS), the polarization index of macrophages was detected, and the supernatant of macrophage medium was extracted as conditioned medium to act on chondrocytes and detect the apoptosis index. The OA model of mice was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity to reduce the expression of Peli1. The degree of cartilage destruction and synovitis were evaluated by haematoxylin and eosin (H&E) staining, Safranin O/Fast Green staining, and immunohistochemistry.Aims
Methods
To assess the alterations in cell-specific DNA methylation associated with chondroitin sulphate response using peripheral blood collected from Kashin-Beck disease (KBD) patients before initiation of chondroitin sulphate treatment. Peripheral blood samples were collected from KBD patients at baseline of chondroitin sulphate treatment. Methylation profiles were generated using reduced representation bisulphite sequencing (RRBS) from peripheral blood. Differentially methylated regions (DMRs) were identified using MethylKit, while DMR-related genes were defined as those annotated to the gene body or 2.2-kilobase upstream regions of DMRs. Selected DMR-related genes were further validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to assess expression levels. Tensor composition analysis was performed to identify cell-specific differential DNA methylation from bulk tissue.Aims
Methods
This study aimed, through bioinformatics analysis, to identify the potential diagnostic markers of osteoarthritis, and analyze the role of immune infiltration in synovial tissue. The gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by R software. Functional enrichment analyses were performed and protein-protein interaction networks (PPI) were constructed. Then the hub genes were screened. Biomarkers with high value for the diagnosis of early osteoarthritis (OA) were validated by GEO datasets. Finally, the CIBERSORT algorithm was used to evaluate the immune infiltration between early-stage OA and end-stage OA, and the correlation between the diagnostic marker and infiltrating immune cells was analyzed.Aims
Methods
Rheumatoid arthritis (RA) is a common chronic immune disease. Berberine, as its main active ingredient, was also contained in a variety of medicinal plants such as Berberaceae, Buttercup, and Rutaceae, which are widely used in digestive system diseases in traditional Chinese medicine with anti-inflammatory and antibacterial effects. The aims of this article were to explore the therapeutic effect and mechanism of berberine on rheumatoid arthritis. Cell Counting Kit-8 was used to evaluate the effect of berberine on the proliferation of RA fibroblast-like synoviocyte (RA-FLS) cells. The effect of berberine on matrix metalloproteinase (MMP)-1, MMP-3, receptor activator of nuclear factor kappa-Β ligand (RANKL), tumour necrosis factor alpha (TNF-α), and other factors was determined by enzyme-linked immunoassay (ELISA) kit. Transcriptome technology was used to screen related pathways and the potential targets after berberine treatment, which were verified by reverse transcription-polymerase chain reaction (RT-qPCR) and Western blot (WB) technology.Aims
Methods
The aims of this study were to determine the incidence and factors for developing periprosthetic joint infection (PJI) following hemiarthroplasty (HA) for hip fracture, and to evaluate treatment outcome and identify factors associated with treatment outcome. A retrospective review was performed of consecutive patients treated for HA PJI at a tertiary referral centre with a mean 4.5 years’ follow-up (1.6 weeks to 12.9 years). Surgeries performed included debridement, antibiotics, and implant retention (DAIR) and single-stage revision. The effect of different factors on developing infection and treatment outcome was determined.Aims
Methods
Mendelian randomization (MR) is considered to overcome the bias of observational studies, but there is no current meta-analysis of MR studies on rheumatoid arthritis (RA). The purpose of this study was to summarize the relationship between potential pathogenic factors and RA risk based on existing MR studies. PubMed, Web of Science, and Embase were searched for MR studies on influencing factors in relation to RA up to October 2022. Meta-analyses of MR studies assessing correlations between various potential pathogenic factors and RA were conducted. Random-effect and fixed-effect models were used to synthesize the odds ratios of various pathogenic factors and RA. The quality of the study was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology using Mendelian Randomization (STROBE-MR) guidelines.Aims
Methods
Introduction. Version abnormalities of the femur, either retroversion or excessive anteversion, cause pain and hip
Exosomes (exo) are involved in the progression of osteoarthritis (OA). This study aimed to investigate the function of dysfunctional chondrocyte-derived exo (DC-exo) on OA in rats and rat macrophages. Rat-derived chondrocytes were isolated, and DCs induced with interleukin (IL)-1β were used for exo isolation. Rats with OA (n = 36) or macrophages were treated with DC-exo or phosphate-buffered saline (PBS). Macrophage polarization and autophagy, and degradation and chondrocyte activity of cartilage tissues, were examined. RNA sequencing was used to detect genes differentially expressed in DC-exo, followed by RNA pull-down and ribonucleoprotein immunoprecipitation (RIP). Long non-coding RNA osteoarthritis non-coding transcript (OANCT) and phosphoinositide-3-kinase regulatory subunit 5 (PIK3R5) were depleted in DC-exo-treated macrophages and OA rats, in order to observe macrophage polarization and cartilage degradation. The PI3K/AKT/mammalian target of rapamycin (mTOR) pathway activity in cells and tissues was measured using western blot.Aims
Methods
Aims. To compare radiographic failure and re-operation rates of anatomical
coracoclavicular (CC) ligament reconstructional techniques with
non-anatomical techniques after chronic high grade acromioclavicular
(AC)
Acute septic arthritis of the knee can lead to
Hip arthroscopy is particularly attractive in
children as it confers advantages over arthrotomy or open surgery,
such as shorter recovery time and earlier return to activity. Developments
in surgical technique and arthroscopic instrumentation have enabled
extension of arthroscopy of the hip to this age group. Potential
challenges in paediatric and adolescent hip arthroscopy include
variability in size, normal developmental change from childhood to
adolescence, and conditions specific to children and adolescents
and their various consequences. Treatable disorders include the
sequelae of traumatic and sports-related hip
Septic arthritis is a therapeutic emergency with a high mortality rate (about 11%)(1). Inadequate treatment can cause permanent
Young adults with hip pain secondary to femoroacetabular
impingement (FAI) are rapidly being recognised as an important cohort
of orthopaedic patients. Interest in FAI has intensified over the
last decade since its recognition as a precursor to arthritis of
the hip and the number of publications related to the topic has
increased exponentially in the last decade. Although not all patients
with abnormal hip morphology develop osteoarthritis (OA), those
with FAI-related
Introduction. In this study we decided to observe the incidence of osteoarthritis following ORIF of Lisfranc
Rheumatoid arthritis (RA) is an autoimmune disease characterized by symmetrical and chronic polyarthritis. Fibroblast-like synoviocytes are mainly involved in joint inflammation and cartilage and bone destruction by inflammatory cytokines and matrix-degrading enzymes in RA. Approaches that induce various cellular growth alterations of synoviocytes are considered as potential strategies for treating RA. However, since synoviocytes play a critical role in RA, the mechanism and hyperplastic modulation of synoviocytes and their motility need to be addressed. In this review, we focus on the alteration of synoviocyte signalling and cell fate provided by signalling proteins, various antioxidant molecules, enzymes, compounds, clinical candidates, to understand the pathology of the synoviocytes, and finally to achieve developed therapeutic strategies of RA. Cite this article:
Osteoarticular loss in a major weightbearing joint is one of the many consequences of military conflict. While minor in terms of life and limb salvage, when rehabilitation is being planned, a small amount of
We have reviewed 41 children under 15 years of age with a fracture of the radius and disruption of the inferior radio-ulnar joint. Despite the fact that the
Introduction. Lisfranc
Introduction: Hot swollen knee joints are a common presentation in clinical practice. It has wide differential diagnoses, the most serious being septic arthritis. Delayed or inadequate treatment leads to
Rheumatoid arthritis (RA), which mainly results from fibroblast-like synoviocyte (FLS) dysfunction, is related to oxidative stress. Advanced oxidation protein products (AOPPs), which are proinflammatory mediators and a novel biomarker of oxidative stress, have been observed to accumulate significantly in the serum of RA patients. Here, we present the first investigation of the effects of AOPPs on RA-FLSs and the signalling pathway involved in AOPP-induced inflammatory responses and invasive behaviour. We used different concentrations of AOPPs (50 to 200 µg/ml) to treat RA-FLSs. Cell migration and invasion and the expression levels of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), and MMP-13 were investigated. Western blot and immunofluorescence were used to analyze nuclear factor-κB (NF-κB) activation.Aims
Methods
1 . A specific mechanism of injury can produce a tear of the articular disc of the wrist without any associated bony lesion. 2. Torn discs have been found associated with Colles's fractures and with dislocation of the inferior radio-ulnar joint. 3. The injury gives rise to clear-cut symptoms and definite physical signs. 4. Operation in fourteen cases has shown five types of tear of the disc. 5. Arthrographs of the wrist are helpful in establishing the diagnosis. 6. In isolated tears removal ofthe disc relieves the symptoms and does not prejudice function. 7. If there is other
1. Twenty cases of tarso-metatarsal
Introduction: Early treatment with antibiotics is advocated in the management of septic arthritis. Whilst some argue for mandatory arthrotomy we have used arthrotomy selectively. The results of this approach over a ten year period were reported 20-years ago. Aim: To review the outcome of joint aspiration and selective rather than mandatory arthrotomy for the management of septic arthritis in children. Method: We compared the outcome for cases of septic arthritis in children reported from this centre in the decade 1982–1991 (Group I) with a contemporary cohort, from 1997–2006 (Group II) using the same criteria for diagnosis and the same treatment principles. Results: Group I comprised 61 children, Group II 42. The mean incidence of septic arthritis in children (<
13 years old) was similar for Groups I and II (2.9/100,000 and 3.1/100,000). Infection caused by Haemophilus species declined from 10 of 56 (18%) in Group I to none in Group II. Staphylococcus Aureus reduced from 27/56(48%) in Group I to 13(31%) in Group II. As previously, infections particularly of the infant hip were at highest risk of causing permanent
Purpose of the Study:. Spontaneous intraarticular haemorrhages are the most frequent bleeding episodes encountered in the haemophiliac population, causing pain, joint deformity and arthropathy. Chronic haemophiliac arthropathy is characterised by persistent joint swelling, proliferative synovitis, and damage to or loss of articular cartilage. Elimination of the synovitis is the key to prevention of recurrent intraarticular haemorrhages and
Introduction: Unstable Lisfranc (tarsometatarsal)
Osteoarthritis (OA) is a disease of the joints stemming from a variety of factors, including
Objectives: Injury is a major cause of morbidity in children, but can be prevented if at-risk groups are identified and proper precautions taken. Our study aims to identify the patterns of paediatric fractures in terms of at-risk bone, age, type of fracture, seasonal variations and attempts to look at the role of prevention. Methods: Retrospective study of the children with fractures presented to A&
E and admitted to the paediatric ward at the University Hospital of Hartlepool during August 2004 to August 2005. As used elsewhere we categorised data into injury types. Results: From the total of 1067 children reviewed,564 were boys and 503, girls. Age incidence-highest in the group of 10–14 years (462), with highest presentation in April, May, June months. Of all orthopaedic injuries, 918 were closed fractures, 38 – open fractures, 40 – dislocations, 71-
Introduction. Lisfranc
Between 1985 and 1994, 1223 patients with malleolar fractures of the ankle were treated by open reduction and internal fixation with absorbable pins and screws, of whom 74 (6.1%) had an obvious inflammatory foreign-body reaction to the implants. Of these 74, ten later developed moderate to severe osteoarthritis of the ankle despite no evidence of incongruity of the articular surface. The implants used in these patients were made from polyglycolide, polylactide or glycolidelactide copolymer. The
Our work is based on the analysis of 104 patients with suppurative posttraumatic osteoarthritis of the ankle joint. By prolonged septic arthritis with degradation of articular surfaces of ankle and shin bones we used necrectomia with osteoarthrotomy and compression arthrodesis in the mechanism of external fixation, which allows to radically sanify the nidus of infection and eliminate the inflammatory process all together. This operation was performed for 68 patients. Surgical treatment for 18 patients with septic arthritis of the ankle joint with considerable involvement of ankle joint metaepiphysis was performed in the following way. We performed segmental resection of the shin bone distal part, put in external fixation mechanism with the possibility of defect building, and then we performed the osteotomy of the shin bone in its upper one-third. On the 10th day we started performing building of defect by Ilizarov. For six patients with ankle joint septic arthritis with considerable involvement of ankle bone we performed its subtotal resection and compression arthrodesis in the external fixation mechanism. For patients with total overall affection of the ankle bone we performed ankle bone excision and tibialcalcaneal fusion. For three patients we performed ankle bone excision with tibialcalcaneal fusion and external fixation. For nine patients where it was not possible to perform a single-stage fusion of shin and heel bones we used external fixation mechanism with the possibility to move the shin bone fragment. Then we performed open fusion of shin and heel bones. The result was considered to be position (92% of patients) in case of extremity support ability recovery, suppurative process elimination and bony ankylosis achievement. Original ankle
Introduction: Treatment of choice in osteogenesis imperfecta (O.I.) patients presenting severe deformities of lower limbs is endomedular nailing with previous corrective osteotomy. Fassier-Duval telescopic rod permits anterograde nailing without the need of distal arthrotomy and thus,
Summary Statement. Using a weight-bearing force control task, age-related changes in muscle action were observed in osteoarthritic subjects, however, greater activation of rectus femoris and medial hamstring muscles in the OA group compared to control indicates greater cocontraction and varied stabilisation strategies. Introduction. Osteoarthritis (OA) is the most debilitating condition among older adults. OA is thought to be mechanically driven by altering the stabilising integrity of the joint. The main contributor to knee joint stability is that of muscular contraction. In cases where the history of a traumatic knee
Knowledge of joint kinematics in the lower limb is important for understanding
The correction of axial deviation of the lower limbs in paediatric patients requires complete patient history and clinical examination. The correct approach to the deformity must consider:radiology,evolution,associated
We present an all arthroscopic technique for modified Weaver Dunn reconstruction of symptomatic chronic type III ACJ
Summary Statement. IL-1β stimulation of human OA chondrocytes induces NFκB, ERK1/2, c-JUN, IκB and P38 signalling pathways. Pre-treatment with cannabinoid WIN-55 for 48 hours inhibits certain pathways, providing mechanisms for cannabinoids inhibitory actions on IL-1β induced cartilage degradation. Matrix metalloproteinases (MMPs) are involved in extracellular matrix (ECM) breakdown in osteoarthritis (OA) and their expression is regulated by nuclear factor kappa B (NFκB). In addition signalling pathways ERK1/2, c-JUN, IκB and P38 are activated in OA and are induced by inflammatory cytokine interleukin 1 (IL-1). Cannabinoids have been shown to reduce
Introduction:. The sealing function of the acetabular labrum is central to the stability of the hip and the health of the joint. Disruption of the labrum has been shown to reduce intra-articular pressure and increase the rate of cartilage consolidation during static loading. Functional activities require movement of the hip through wide ranges of joint motion which disrupt joint congruency, and thus may alter the seal. This study was performed to test the hypothesis that the sealing function of the labrum varies with the position of the hip during functional activities. Methods:. Six fresh cadaveric hip joint specimens were obtained from donors of average age 45.5 ± 16.1 years (range 25–63 years). Each specimen was dissected free of soft tissue, leaving the capsule and labrum intact, potted in mounting fixtures, and placed in a loading apparatus. Catheters were inserted into the central and peripheral compartments of each hip to allow infusion of fluid and monitoring of compartment pressures via miniature transducers (OMEGA Engineering, Inc). After application of a joint load of 0.50 BW, fluid was introduced into the central compartment at a constant rate until transport was indicated by a rise in pressure within the peripheral compartment. These measurements were performed with each hip placed in 10 functional positions ranging from −5 to 105 degrees of flexion, −5 to 13 degrees of abduction, and −25 to 35 degrees of external rotation simulating the sequential stages of gait, stooping, and pivoting. Motion analysis was performed via reflective marker arrays attached to the femur and pelvis to allow computer visualization of the position of the pelvis and femur using CT reconstructions. In each hip position, we measured the peak pressure (kPA) developed within the central compartment prior to fluid transfer to the peripheral compartment. Results:. The sealing capacity of the labrum varied wit hip joint position (p = 0.003). Peak pressures were greatest during pivoting (average peak central compartment pressure: 33.9 ± 5.0 kPa; p = 0.001), compared to both gait (22.5 ± 4.1 kPa; p = 0.047) and stoop (9.6 ± 3.6 kPa; p = 0.004). During the pivoting maneuver, peak pressures increased in a linear fashion with increasing hip extension and external rotation. Conversely, the sealing capacity of the labrum was reduced during stooping once hip flexion exceeded 70° and internal rotation was greater than 15°. The positions simulating gait consisted of minimal to no joint rotation, and peak pressures varied little between the four positions. Discussion:. The sealing ability of the labral seal increases with external rotation of the hip joint, and decreases with increased flexion combined with internal rotation. Changes in joint congruency that occur when the hip is placed in high flexion and internal rotation may be responsible for the loss of sealing function of the labrum during stooping. Our results reveal the importance of joint position during functional activities on the ability of the labrum to seal the central compartment of the hip. Future research will further assess the relationship between these positions and
Objectives:. Experimental disruption of the labrum has been shown to compromise its sealing function and alter cartilage lubrication. However, it is not known whether pathological changes to the labrum secondary to femoro-acetabular impingement (FAI) have a similar impact on labral function. This study was performed to determine the effect of natural labral damage secondary to abnormal femoral morphology on the labral seal. Methods:. Ten intact hip specimens were obtained from male donors (47.8 ± 1.5 yrs) for use in this study. CT reconstructions demonstrated that 6 specimens were of normal morphology, while 4 displayed morphology typical of cam-FAI. Specimens were dissected free of the overlying soft tissue, leaving the capsule and labrum intact. Each specimen was potted and placed in a loading apparatus (0.5 BW). Pressures developed within the central and peripheral compartments were monitored with miniature pressure transducers. The sealing capacity of the labrum was measured by introducing fluid into the central compartment at a constant rate until transport was detected from the central to the peripheral compartment. These measurements were performed in 10 functional positions simulating sequential stages of gait, stooping, and pivoting. During testing, the 3D motion of the femoral head in the acetabulum was measured with motion analysis combined with computer visualization. Peak pressures were compared between specimens with and without labral damage for each of the three activities (p < 0.05). Results:. Visual observation following testing showed that each specimen with CAM morphology exhibited secondary damage of the labrum and the adjacent chondral surface, while specimens of normal morphology were undamaged. Average peak central compartment pressure was affected by the presence of labral damage secondary to impingement. The specimens with labral damage exhibited reduced peak central compartment pressure during pivot (15.2 ± 2.6 vs. 42.3 ± 7.7 kPa; p = 0.007) when compared to intact specimens. Conversely, no differences in peak pressure were detected between specimens with and without labral damage during simulated gait (21.1 ± 6.0 vs. 22.0 ± 4.2 kPA; p = 0.9) and stooping (8.6 ± 2.4 vs. 7.5 ± 2.6 kPa; p = 0.78). Conclusions:. The acetabular seal, quantified by intra-articular pressure, was affected by the presence of labral damage secondary to impingement. The reduction in ultimate pressure occurred during pivoting; however, the seal was maintained during gait and stooping. These results are in contrast to previous studies which reported a complete negation of the seal in response to experimentally-created labral disruption. As degeneration is progressive with repetitive impingement, loss of the seal starts to be seen during pivoting and may progress from there, but at this time point (50 years), the seal remains intact during gait and stooping. Our study highlights the importance of using clinically relevant
Summary. The ideal therapy for post-traumatic osteoarthritis (PTOA) must be mechanism-based and target multiple anabolic and catabolic pathways. Our results suggest an innovative combination of known pro-anabolic and anti-catabolic biologics to treat post-traumatic cartilage degeneration. Introduction. Untreated
Introduction and aims: Osteoarthritis (OA) of the knee is a widespread problem, yet there is little known about the kinematics of the osteoarthritic knee, and nothing about the tibio-femoral contact pattern. This study aimed to describe the role of tibio-femoral interface events in articular surface wear and degenerative change. Method: Fourteen subjects with symptomatic OA in one knee, and no pain or injury in the contralateral knee were recruited. The tibio-femoral contact pattern was recorded for both knees, while performing a supine leg-press from 0 to 90 degrees flexion against a 150N load. Severity of osteoarthritis was measured by Kellgren Lawrence grade, bone mineral density (BMD) using Dual Energy X-ray Absorptiometry close to the subchondral bone, diagnostic MRI, and
Background. Osteoarthritis (OA), is characterised with a loss of cartilage and pain in affected joints. It is this pain which most patients associate with their condition. Intra-articular (IA) hyaluronan (HA) has been shown to reduce the pain associated with OA both in animal models and in clinical trials. There are purified HA available and in recent years hyaluronan hydrogels, where the material has been cross-linked into networks, have become available. One of these cross-linked HA hydrogels is Durolane¯. This study has sought to evaluate the effect of Durolane in an in vivo model of osteoarthritis. Methods. Mice (C57BL/6, 12 weeks) were obtained from Jackson Labs and all protocols were approved by Rush IACUC.
Introduction: Acromioclavicular (AC)
Poly (ADP-ribose) polymerase (PARP) inhibitor has been reported to attenuate inflammatory response in rat models of inflammation. This study was designed to investigate the effect of PARP signalling in osteoarthritis (OA) cartilage inflammatory response in an OA rat model. The OA model was established by anterior cruciate ligament transection with medial meniscectomy in Wistar rats. The poly (ADP-ribose) polymerase 1 (PARP-1) shRNA (short hairpin (sh)-PARP-1) and negative control shRNA (sh-NC) were delivered using a lentiviral vector and were intra-articularly injected into rats after surgery. The weight-bearing distribution of the hind limbs and the knee joint width were measured every two weeks. The expression levels of PARP-1, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in cartilage were determined using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. The serum concentrations of inflammatory cytokines were detected using enzyme-linked immunosorbent assay (ELISA).Aims
Methods
Purpose: Recurrent hemarthrosis is a common clinical entity in hemophiliacs. They not only interfere with daily life but also trigger hemophilic arthropathy. Synovial hypertrophy has a pivot role in hemarthrosis related
Osteoarthritis (OA) involves pathology in both articular cartilage and subchondral bone. The osteoprotegerin (OPG)/receptor activator of nuclear factor kappa beta ligand (RANK-L) balance is known to modulate bone turnover. We compared the bony changes in human total knee arthroplasty (TKA) and cadaveric controls. A qualitative increase in subchondral and ligamentous insertional bone mineral density was observed on micro-CT sections of TKA bone compared with cadaveric controls. In-situ hybridization of digoxygenase (DIG)-labelled OPG riboprobes showed selective uptake in osteoblasts but not osteocytes or osteoclasts in TKA bone. Those data suggested that the upregulation of OPG expression by osteoblasts may have precipitated the bony hypertrophy of end-stage OA. Altered joint mechanics produced by periarticular bone remodelling may precede the cartilage changes of osteoarthritis (OA). Recently, receptor activator of nuclear factor kappa beta (RANK), along with its soluble ligand (RANK-L), have been shown to induce both maturation and activation of bone-degrading osteoclasts. Activation of RANK on osteoclast cells by RANK-L is opposed by another soluble factor, osteoprotegerin (OPG). Thus RANK/OPG balance is important in regulating bone turnover. Here, we compared periarticular bone from patients with end-stage OA undergoing total knee arthroplasty (TKA) with those of cadaveric controls. We assessed bony, histological and molecular changes that are important in the pathogenesis of OA. Using in-situ hybridization, we found increased staining of digoxygenase (DIG)-labelled OPG in osteoblasts of TKA bone. A corresponding increase in subchondral and insertional bone was seen on micro-CT (μCT) sections from TKA bone in comparison with cadaveric controls. Those changes were accompanied by marked articular cartilage degeneration on histology. This study is the first of which we are aware that directly assessed the role of OPG in inducing the bony changes seen in human end-stage OA. We used μCT to compare corresponding samples qualitatively from TKA and cadaveric bone. Adjacent sections underwent hybridization of digoxygenase (DIG)-labelled OPG riboprobes to assess gene expression in situ. Finally, samples were stained and analysed for histology. Bony hypertrophy may be a result of overexpression of OPG that occurs as an important feature of OA pathophysiology. Funding: This work was supported by a grant from the Hip Hip Hooray Fund of the Canadian Orthopaedic Research Foundation (CORF) and the Wood Professorship in
Osteoarthritis is a slowly progressive musculoskeletal disorder that can occur in any joint and is characterised by symptoms of pain, stiffness or loss of function. Studies showed that the work related disability rate with osteoarthritis varied from 30 to 50%, it is also a frequent cause of early retirement. Age is the strongest predictor of the development and progression of radiographic osteoarthritis. Further risk factors are physical activity, injuries, high bone mass index and intensive sport activities. Targets that are most important in the prevention or management of osteoarthritis are to reduce pain, disability and to prevent radiological progression. There are various life style factors that increase the risk of developing osteoarthritis, increase its rate of progression and may increase pain and functional limitation. Preventable or modifyable risk factors are obesity and mechanical aspects of the joint f.e. joint laxity or malalignment. Tears of menisci or ligaments may lead to at normal loading of articular cartilage and result in the increased deveopment of osteoarthritis. Further risk factors are certain occupations (f.e. farmers for hip- and knee osteoarthritis), intensive sport participation, muscle weakness and nutritional factors. Pharmacological interventions are mainly to treat the symptom of pain and have nearly no effect on tissue damage. Nevertheless activity and participation is improved as well as using simple analgesics, antiinflammatory drugs, disease modifying therapies, hyaluronic acid and intraarticular steroids. There is no evidence that pharmacological interventions can prevent osteoarthritis as defined by radiological changes. Biomechanic deficiencies may lead to
Interleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism. Porcine nucleus pulposus (NP) cells were treated with vehicle, 10 ng/ml IL-1β, 10 μM suramin, or 10 μM suramin plus IL-1β. The expression levels of catabolic and anabolic proteins, proinflammatory cytokines, mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB-related signalling molecules were assessed by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence analysis. Flow cytometry was applied to detect apoptotic cells. The ex vivo effects of suramin were examined using IDD organ culture and differentiation was analyzed by Safranin O-Fast green and Alcian blue staining.Aims
Methods
Methods of study: Prospective Controlled Animal Study. Objectives: Evaluation of the feasibility of embryonal epiphyses transplantation in a xenogeneic model for reconstruction of adult articular cartilage in a rabbit model. Introduction: Articular cartilage reconstruction has been the goal for many years of orthopaedic research. Current acceptable techniques include the use of allografts, autologous chondrocytes transplantation and osteochondral cylinder grafting. Reconstruction of articular cartilage defects using adult osteochondral allografts is an established clinical procedure, whose principal drawback is lack of lateral integration of the grafts to the surrounding tissue. Autologous chondrocytes transplantation is a sophisticated technique requiring cell culture and a staged operation. Its main draw back is the lack of mechanical strength early on and the prolonged rehabilitation period. This study was conducted in order to evaluate the possibility of using embryonal epiphyses as a cartilage reconstruction tissue. Methods: A xenogeneic human to rabbit sub-acute osteochondral defect model was designed to evaluate the possibility of allogeneic implantation in humans. The following procedures were performed (n=5): transplantation of: 1. live epiphyses, 2. live epiphyses with autogeneic periosteum, 3. devitalized epiphyses, and 4. devitalized epiphyses with autogeneic articular chondrocytes. A fifth control group did not receive any implant. Animals were followed for 3 months after transplantation and than sacrificed. The histological specimens were evaluated by image analysis after immuno-histochemical stains were performed (including the following antigens – collagen type II, collagen type I, collagen type III, collagen type X, S-100, alkaline phosphatase, osteocalcin, osteopontin, nitric oxide synthase). Results: Animals in groups 1 and 2 had a viable reconstruction of the articular surface with little evidence of rejection and without pannus formation. Animals in groups 3 and 4 became severely arthrotic and the graft was resorbed. Nitric oxide synthase accumulation was reduced in group 1 and 2 as compared to groups 3, 4, and 5, indicating a joint preserving function of the epiphyseal grafts. Discussion: Epiphyseal grafts appear to be a feasible procedure for reconstruction of articular cartilage defects even in a xenogeneic model. The restoration of articular cartilage even with a xenogeneic graft appears to prevent nitric oxide synthesis and the resulting destruction of unafflicted articular cartilage. This is a major pathway leading to secondary osteoarthritis after
Background and Purpose: There is a high incidence of arthritis in the hand, but joint replacement technology in the wrist and other small joints is still in its infancy compared with the larger joints. The wrist is the most complex small joint and so there is a need for fundamental research into the way in which it works. At present there is no generally agreed upon satisfactory explanation for the complex movement patterns of the carpal bones. The purpose of the work was to test a new hypothesis on wrist kinematics. The basis of the hypothesis was that the bones of the wrist move in such a manner as to maximise total contact area in the joint, thereby minimising contact stress. Such a strategy would minimise the bone mass requirements, thereby minimising the biological “cost” of creating and maintaining the joint. This agrees with the minimum energy principle, which governs many natural processes. Methods: A computer model was created to test the hypothesis. A cadaveric wrist was dissected and 3D faceted models of the carpal bones were created using laser digitisation. The model contained a program to evaluate the closeness of packing of the carpal bones and an optimisation algorithm [. 1. ] to maximise this quantity by adjusting the positions of the bones. The evaluation program computed the contact area and level of intersection between nine pairs of interacting bones. Rotation in the radial-ulnar deviation plane was applied in 1.0° increments to four rigidly connected bones defining the overall posture of the wrist, and an optimisation algorithm was used to maximise the contact area by adjusting the positions and orientations of the remaining bones. Results: The results of the work are encouraging because certain known characteristics of carpal behaviour were clearly predicted by the model. The results for the scaphoid in particular were similar to the characteristic movements of this bone in both radial and ulnar deviation. During 20° of unlar deviation, the bone demonstrated 14.3° of extension, which is near to the 20.4° reported by an experimental study [. 2. ]. In 10° of radial deviation, the bone underwent 6.4° of flexion, which again is close to the 8.1° experimental result. Conclusion: Although the computer model predicted certain aspects of carpal behaviour, the initial hypothesis was not conclusively proved. This is due in part to the computational complexity of the task. Despite some simplifying assumptions, there were still a large number of degrees of freedom, and it is almost certain that the optimisation process was afflicted with local minima problems. If the technical hurdles can be overcome and the hypothesis is proved correct, then we will gain a new explanation of the laws governing the kinematics of the wrist joint, which are not fully understood at present. This will provide invaluable information for surgical applications, where a thorough understanding of normal kinematics is essential for the treatment of
The aim of this study was to determine the extent to which patient demographics, clinical presentation, and blood parameters vary in A prospective case series was undertaken at a single UK paediatric institution between October 2012 and November 2018 of all patients referred with suspected septic arthritis. We recorded the clinical, biochemical, and microbiological findings in all patients.Aims
Methods
Tenosynovial giant cell tumour (TGCT) is one of the most common soft-tissue tumours of the foot and ankle and can behave in a locally aggressive manner. Tumour control can be difficult, despite the various methods of treatment available. Since treatment guidelines are lacking, the aim of this study was to review the multidisciplinary management by presenting the largest series of TGCT of the foot and ankle to date from two specialized sarcoma centres. The Oxford Tumour Registry and the Leiden University Medical Centre Sarcoma Registry were retrospectively reviewed for patients with histologically proven foot and ankle TGCT diagnosed between January 2002 and August 2019.Aims
Methods
This study aimed to investigate whether human umbilical cord mesenchymal stem cells (UC-MSCs) can prevent articular cartilage degradation and explore the underlying mechanisms in a rat osteoarthritis (OA) model induced by monosodium iodoacetate (MIA). Human UC-MSCs were characterized by their phenotype and multilineage differentiation potential. Two weeks after MIA induction in rats, human UC-MSCs were intra-articularly injected once a week for three weeks. The therapeutic effect of human UC-MSCs was evaluated by haematoxylin and eosin, toluidine blue, Safranin-O/Fast green staining, and Mankin scores. Markers of joint cartilage injury and pro- and anti-inflammatory markers were detected by immunohistochemistry.Aims
Methods
Rheumatoid arthritis (RA) is a systematic autoimmune disorder, characterized by synovial inflammation, bone and cartilage destruction, and disease involvement in multiple organs. Although numerous drugs are employed in RA treatment, some respond little and suffer from severe side effects. This study aimed to screen the candidate therapeutic targets and promising drugs in a novel method. We developed a module-based and cumulatively scoring approach that is a deeper-layer application of weighted gene co-expression network (WGCNA) and connectivity map (CMap) based on the high-throughput datasets.Aims
Methods