Aims. The association of auraptene (AUR), a 7-geranyloxycoumarin, on osteoporosis and its potential pathway was predicted by network pharmacology and confirmed in experimental osteoporotic mice. Methods. The network of AUR was constructed and a potential pathway predicted by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) terms enrichment. Female ovariectomized (OVX) Institute of Cancer Research mice were intraperitoneally injected with 0.01, 0.1, and 1 mM AUR for four weeks. The bone mineral density (BMD)
Aims. Long non-coding RNAs (lncRNAs) act as crucial regulators in osteoporosis (OP). Nonetheless, the effects and potential molecular mechanism of lncRNA PCBP1 Antisense RNA 1 (PCBP1-AS1) on OP remain largely unclear. The aim of this study was to explore the role of lncRNA PCBP1-AS1 in the pathogenesis of OP. Methods. Using quantitative real-time polymerase chain reaction (qRT-PCR), osteogenesis-related genes (alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OPN), and Runt-related transcription factor 2 (RUNX2)), PCBP1-AS1, microRNA (miR)-126-5p, group I Pak family member p21-activated kinase 2 (PAK2), and their relative expression
Aims. Overall sagittal flexion is restricted in patients who have undergone both lumbar fusion and total hip arthroplasty (THA). However, it is not evident to what extent this movement is restricted in these patients and how this influences quality of life (QoL). The purpose of this study was to determine the extent to which hip-lumbar mobility is decreased in these patients, and how this affects their QoL score. Methods. Patients who underwent primary THA at our hospital between January 2010 and March 2021 were considered (n = 976). Among them, 44 patients who underwent lumbar fusion were included as cases, and 44 THA patients without lumbar disease matched by age, sex, and BMI as Control T. Among those who underwent lumbar fusion, 44 patients without hip abnormalities matched by age, sex, and BMI to the cases were considered as Control F. Outcome and spinopelvic parameters were measured radiologically in extension and flexed-seated positions. Hip, lumbar, and hip-lumbar mobility were calculated as parameter changes between positions. Results. There were 20 male and 112 female patients in the case and control groups, with a mean age of 77 years (5 to 94) and a mean BMI of 24 kg/m. 2. (15 to 34). QoL score and hip-lumbar mobility were reduced in cases compared to Control T and F, and were further reduced as the number of fused
Aims. CRP is an acute-phase protein that is used as a biomarker to follow severity and progression in infectious and inflammatory diseases. Its pathophysiological mechanisms of action are still poorly defined. CRP in its pentameric form exhibits weak anti-inflammatory activity. The monomeric isoform (mCRP) exerts potent proinflammatory properties in chondrocytes, endothelial cells, and leucocytes. No data exist regarding mCRP effects in human intervertebral disc (IVD) cells. This work aimed to verify the pathophysiological relevance of mCRP in the aetiology and/or progression of IVD degeneration. Methods. We investigated the effects of mCRP and the signalling pathways that are involved in cultured human primary annulus fibrosus (AF) cells and in the human nucleus pulposus (NP) immortalized cell line HNPSV-1. We determined messenger RNA (mRNA) and protein
Aims. Mechanical stimulation is a key factor in the development and healing of tendon-bone insertion. Treadmill training is an important rehabilitation treatment. This study aims to investigate the benefits of treadmill training initiated on postoperative day 7 for tendon-bone insertion healing. Methods. A tendon-bone insertion injury healing model was established in 92 C57BL/6 male mice. All mice were divided into control and training groups by random digital table method. The control group mice had full free activity in the cage, and the training group mice started the treadmill training on postoperative day 7. The quality of tendon-bone insertion healing was evaluated by histology, immunohistochemistry, reverse transcription quantitative polymerase chain reaction, Western blotting, micro-CT, micro-MRI, open field tests, and CatWalk gait and biomechanical assessments. Results. Our results showed a significantly higher tendon-bone insertion histomorphological score in the training group, and the messenger RNA and protein expression
Anterior cruciate ligament (ACL) injuries are among the most common and debilitating knee injuries in professional athletes with an incidence in females up to eight-times higher than their male counterparts. ACL injuries can be career-threatening and are associated with increased risk of developing knee osteoarthritis in future life. The increased risk of ACL injury in females has been attributed to various anatomical, developmental, neuromuscular, and hormonal factors. Anatomical and hormonal factors have been identified and investigated as significant contributors including osseous anatomy, ligament laxity, and hamstring muscular recruitment. Postural stability and impact absorption are associated with the stabilizing effort and stress on the ACL during sport activity, increasing the risk of noncontact pivot injury. Female patients have smaller diameter hamstring autografts than males, which may predispose to increased risk of re-rupture following ACL reconstruction and to an increased risk of chondral and meniscal injuries. The addition of an extra-articular tenodesis can reduce the risk of failure; therefore, it should routinely be considered in young elite athletes. Prevention programs target key aspects of training including plyometrics, strengthening, balance, endurance and stability, and neuromuscular training, reducing the risk of ACL injuries in female athletes by up to 90%. Sex disparities in access to training facilities may also play an important role in the risk of ACL injuries between males and females. Similarly, football boots, pitches quality, and football size and weight should be considered and tailored around females’ characteristics. Finally, high
Aims. Continuous local antibiotic perfusion (CLAP) has recently attracted attention as a new drug delivery system for orthopaedic infections. CLAP is a direct continuous infusion of high-concentration gentamicin (1,200 μg/ml) into the bone marrow. As it is a new system, its influence on the bone marrow is unknown. This study aimed to examine the effects of high-concentration antibiotics on human bone tissue-derived cells. Methods. Cells were isolated from the bone tissue grafts collected from six patients using the Reamer-Irrigator-Aspirator system, and exposed to different gentamicin concentrations. Live cells rate, apoptosis rate, alkaline phosphatase (ALP) activity, expression of osteoblast-related genes, mineralization potential, and restoration of cell viability and ALP activity were examined by in vitro studies. Results. The live cells rate (the ratio of total number of cells in the well plate to the absorbance-measured number of live cells) was significantly decreased at ≥ 500 μg/ml of gentamicin on day 14; apoptosis rate was significantly increased at ≥ 750 μg/ml, and ALP activity was significantly decreased at ≥ 750 μg/ml. Real-time reverse transcription-polymerase chain reaction results showed no significant decrease in the ALP and activating transcription factor 4 transcript
Aims. The presence of facet tropism has been correlated with an elevated susceptibility to lumbar disc pathology. Our objective was to evaluate the impact of facet tropism on chronic lumbosacral discogenic pain through the analysis of clinical data and finite element modelling (FEM). Methods. Retrospective analysis was conducted on clinical data, with a specific focus on the spinal units displaying facet tropism, utilizing FEM analysis for motion simulation. We studied 318 intervertebral
Aims. Triplane ankle fractures are complex injuries typically occurring in children aged between 12 and 15 years. Classic teaching that closure of the physis dictates the overall fracture pattern, based on studies in the 1960s, has not been challenged. The aim of this paper is to analyze whether these injuries correlate with the advancing closure of the physis with age. Methods. A fracture mapping study was performed in 83 paediatric patients with a triplane ankle fracture treated in three trauma centres between January 2010 and June 2020. Patients aged younger than 18 years who had CT scans available were included. An independent Paediatric Orthopaedic Trauma Surgeon assessed all CT scans and classified the injuries as n-part triplane fractures. Qualitative analysis of the fracture pattern was performed using the modified Cole fracture mapping technique. The maps were assessed for both patterns and correlation with the closing of the physis until consensus was reached by a panel of six surgeons. Results. Fracture map grouped by age demonstrates that, regardless of age (even at the extremes of the spectrum), the fracture lines consolidate in a characteristic Y-pattern, and no shift with closure of the physis was observed. A second fracture map with two years added to female age also did not show a shift. The fracture map, grouped by both age and sex, shows a Y-pattern in all different groups. The fracture lines appear to occur between the anterior and posterior inferior tibiofibular ligaments, and the medially fused physis or deltoid ligament. Conclusion. This fracture mapping study reveals that triplane ankle fractures have a characteristic Y-pattern, and acknowledges the weakness created by the physis, however it also challenges classic teaching that the specific fracture pattern at the
Aims. To examine how eukaryotic translation initiation factor 5A (eIF5A) regulates osteoarthritis (OA) during mechanical overload and the specific mechanism. Methods. Histological experiments used human bone samples and C57BL/6J mice knee samples. All cell experiments were performed using mice primary chondrocytes. Messenger RNA (mRNA) sequencing was performed on chondrocytes treated with 20% cyclic tensile strain for 24 hours. Western blot (WB) and quantitative polymerase chain reaction were employed to detect relevant indicators of cartilage function in chondrocytes. We created the destabilization of the medial meniscus (DMM) model and the mechanical overload-induced OA model and injected with overexpressing eIF5A adenovirus (eIF5A-ADV). Cartilage degeneration was evaluated using Safranin O/Fast Green staining. Relative protein
Aims. Osteoarthritis (OA) is a common degenerative joint disease characterized by chronic inflammatory articular cartilage degradation. Long noncoding RNAs (lncRNAs) have been previously indicated to play an important role in inflammation-related diseases. Herein, the current study set out to explore the involvement of lncRNA H19 in OA. Methods. Firstly, OA mouse models and interleukin (IL)-1β-induced mouse chondrocytes were established. Expression patterns of IL-38 were determined in the synovial fluid and cartilage tissues from OA patients. Furthermore, the targeting relationship between lncRNA H19, tumour protein p53 (TP53), and IL-38 was determined by means of dual-luciferase reporter gene, chromatin immunoprecipitation, and RNA immunoprecipitation assays. Subsequent to gain- and loss-of-function assays, the
Aims. It has been well documented in the arthroplasty literature that lumbar degenerative disc disease (DDD) contributes to abnormal spinopelvic motion. However, the relationship between the severity or pattern of hip osteoarthritis (OA) as measured on an anteroposterior (AP) pelvic view and spinopelvic biomechanics has not been well investigated. Therefore, the aim of the study is to examine the association between the severity and pattern of hip OA and spinopelvic motion. Methods. A retrospective chart review was conducted to identify patients undergoing primary total hip arthroplasty (THA). Plain AP pelvic radiographs were reviewed to document the morphological characteristic of osteoarthritic hips. Lateral spine-pelvis-hip sitting and standing plain radiographs were used to measure sacral slope (SS) and pelvic femoral angle (PFA) in each position. Lumbar disc spaces were measured to determine the presence of DDD. The difference between sitting and standing SS and PFA were calculated to quantify spinopelvic motion (ΔSS) and hip motion (ΔPFA), respectively. Univariate analysis and Pearson correlation were used to identify morphological hip characteristics associated with changes in spinopelvic motion. Results. In total, 139 patients were included. Increased spinopelvic motion was observed in patients with loss of femoral head contour, cam deformity, and acetabular bone loss (all p < 0.05). Loss of hip motion was observed in patients with loss of femoral head contour, cam deformity, and acetabular bone loss (all p < 0.001). A decreased joint space was associated with a decreased ΔPFA (p = 0.040). The presence of disc space narrowing, disc space narrowing > two
Aims. We evaluated the national and regional trends from 2013 to 2022, in the prevalence of Perthes’ disease among adolescent males in South Korea. Methods. This retrospective, nationwide, population-based study included a total of 3,166,669 Korean adolescent males examined at regional Military Manpower Administration (MMA) offices over ten years. Data from the MMA were retrospectively collected to measure the national and regional prevalence per 100,000 and 95% CI of Perthes’ disease according to the year (1 January 2013 to 31 December 2022) and history of pelvic and/or femoral osteotomy in South Korea. Spearman’s correlation analysis was performed to assess the relationship between the Perthes’ disease prevalence and several related factors. Results. The prevalence of Perthes’ disease showed a gradually increasing trend for a ten-year follow-up period from 2013 to 2022 with a mean of 71.17 (95% CI 61.82 to 80.52) per 100,000, ranging from 56.02 (95% CI 48.34 to 63.71) in 2013 to 77.53 (95% CI 67.94 to 87.11) in 2019. The proportion of patients with a Stulberg classification ≥ III ranged from 50.57% in 2015 to 80.08% in 2019, showing a gradually increasing trend. Following the trend for Perthes’ disease, an increase in the proportion of pelvic and/or femoral osteotomies was observed, whereas conservative treatment decreased in adolescent males. For a ten-year follow-up period, the prevalence of Perthes’ disease was highest in provinces, followed by the metropolitan area and Seoul. Conclusion. The prevalence of Perthes’ disease in adolescent males increased over time from 2013 to 2022. In particular, the trend in the prevalence of Perthes’ disease with incongruent hips was significantly associated with overweight and obesity rates among male adolescents with a very high
Aims. In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD. Methods. An in vitro model for oxidative stress-induced injury in NPCs was developed to elucidate the mechanisms underlying the upregulation of DDIT4 expression, activation of the reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NLRP3 signalling pathway, and nucleus pulposus pyroptosis. Furthermore, the mechanism of action of small interfering DDIT4 (siDDIT4) on NPCs in vitro was validated. A triplex hydrogel named siDDIT4@G5-P-HA was created by adsorbing siDDIT4 onto fifth-generation polyamidoamine (PAMAM) dendrimer using van der Waals interactions, and then coating it with hyaluronic acid (HA). In addition, we established a rat puncture IVDD model to decipher the hydrogel’s mechanism in IVDD. Results. A correlation between DDIT4 expression
Aims. 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. Methods. 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
Aims. The aims of this study were to report the outcomes of patients with a complex fracture of the lower limb in the five years after they took part in the Wound Healing in Surgery for Trauma (WHIST) trial. Methods. The WHIST trial compared negative pressure wound therapy (NPWT) dressings with standard dressings applied at the end of the first operation for patients undergoing internal fixation of a complex fracture of the lower limb. Complex fractures included periarticular fractures and open fractures when the wound could be closed primarily at the end of the first debridement. A total of 1,548 patients aged ≥ 16 years completed the initial follow-up, six months after injury. In this study we report the pre-planned analysis of outcome data up to five years. Patients reported their Disability Rating Index (DRI) (0 to 100, in which 100 = total disability), and health-related quality of life, chronic pain scores and neuropathic pain scores annually, using a self-reported questionnaire. Complications, including further surgery related to the fracture, were also recorded. Results. A total of 1,015 of the original patients (66%) provided at least one set of outcome data during the five years of follow-up. There was no evidence of a difference in patient-reported disability between the two groups at five years (NPWT group mean DRI 30.0 (SD 26.5), standard dressing group mean DRI 31.5 (SD 28.8), adjusted difference -0.86 (95% CI -4.14 to 2.40; p = 0.609). There was also no evidence of a difference in the complication rates at this time. Conclusion. We found no evidence of a difference in disability ratings between NPWT compared with standard wound dressings in the five years following the surgical treatment of a complex fracture of the lower limb. Patients in both groups reported high
Aims. We aimed to determine the concentrations of synovial vancomycin and meropenem in patients treated by single-stage revision combined with intra-articular infusion following periprosthetic joint infection (PJI), thereby validating this drug delivery approach. Methods. We included 14 patients with PJI as noted in their medical records between November 2021 and August 2022, comprising eight hip and seven knee joint infections, with one patient experiencing bilateral knee infections. The patients underwent single-stage revision surgery, followed by intra-articular infusion of vancomycin and meropenem (50,000 µg/ml). Synovial fluid samples were collected to assess antibiotic concentrations using high-performance liquid chromatography. Results. The peak concentrations of vancomycin and meropenem in the joint cavity were observed at one hour post-injection, with mean values of 14,933.9 µg/ml (SD 10,176.3) and 5,819.1 µg/ml (SD 6,029.8), respectively. The trough concentrations at 24 hours were 5,495.0 µg/ml (SD 2,360.5) for vancomycin and 186.4 µg/ml (SD 254.3) for meropenem. The half-life of vancomycin was 6 hours, while that of meropenem ranged between 2 and 3.5 hours. No significant adverse events related to the antibiotic administration were observed. Conclusion. This method can achieve sustained high antibiotic concentrations within the joint space, exceeding the reported minimum biofilm eradication concentration. Our study highlights the remarkable effectiveness of intra-articular antibiotic infusion in delivering high intra-articular concentrations of antibiotics. The method provided sustained high antibiotic concentrations within the joint cavity, and no severe side-effects were observed. These findings offer evidence to improve clinical treatment strategies. However, further validation is required through studies with larger sample sizes and higher
Aims. Paediatric triplane fractures and adult trimalleolar ankle fractures both arise from a supination external rotation injury. By relating the experience of adult to paediatric fractures, clarification has been sought on the sequence of injury, ligament involvement, and fracture pattern of triplane fractures. This study explores the similarities between triplane and trimalleolar fractures for each stage of the Lauge-Hansen classification, with the aim of aiding reduction and fixation techniques. Methods. Imaging data of 83 paediatric patients with triplane fractures and 100 adult patients with trimalleolar fractures were collected, and their fracture morphology was compared using fracture maps. Visual fracture maps were assessed, classified, and compared with each other, to establish the progression of injury according to the Lauge-Hansen classification. Results. Four stages of injury in triplane fractures, resembling the adult supination external rotation Lauge-Hansen stages, were observed. Stage I consists of rupture of the anterior syndesmosis or small avulsion of the anterolateral tibia in trimalleolar fractures, and the avulsion of a larger Tillaux fragment in triplanes. Stage II is defined as oblique fracturing of the fibula at the
Aims. Therapeutic agents that prevent chondrocyte loss, extracellular matrix (ECM) degradation, and osteoarthritis (OA) progression are required. The expression
Aims. Trained immunity confers non-specific protection against various types of infectious diseases, including bone and joint infection. Platelets are active participants in the immune response to pathogens and foreign substances, but their role in trained immunity remains elusive. Methods. We first trained the innate immune system of C57BL/6 mice via intravenous injection of two toll-like receptor agonists (zymosan and lipopolysaccharide). Two, four, and eight weeks later, we isolated platelets from immunity-trained and control mice, and then assessed whether immunity training altered platelet releasate. To better understand the role of immunity-trained platelets in bone and joint infection development, we transfused platelets from immunity-trained mice into naïve mice, and then challenged the recipient mice with Staphylococcus aureus or Escherichia coli. Results. After immunity training, the
