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Bone & Joint Research
Vol. 13, Issue 11 | Pages 659 - 672
20 Nov 2024
Mo H Sun K Hou Y Ruan Z He Z Liu H Li L Wang Z Guo F

Aims

Osteoarthritis (OA) is a common degenerative disease. PA28γ is a member of the 11S proteasome activator and is involved in the regulation of several important cellular processes, including cell proliferation, apoptosis, and inflammation. This study aimed to explore the role of PA28γ in the occurrence and development of OA and its potential mechanism.

Methods

A total of 120 newborn male mice were employed for the isolation and culture of primary chondrocytes. OA-related indicators such as anabolism, catabolism, inflammation, and apoptosis were detected. Effects and related mechanisms of PA28γ in chondrocyte endoplasmic reticulum (ER) stress were studied using western blotting, real-time polymerase chain reaction (PCR), and immunofluorescence. The OA mouse model was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity of 15 12-week-old male mice to reduce the expression of PA28γ. The degree of cartilage destruction was evaluated by haematoxylin and eosin (HE) staining, safranin O/fast green staining, toluidine blue staining, and immunohistochemistry.


Aims

This study examined the relationship between obesity (OB) and osteoporosis (OP), aiming to identify shared genetic markers and molecular mechanisms to facilitate the development of therapies that target both conditions simultaneously.

Methods

Using weighted gene co-expression network analysis (WGCNA), we analyzed datasets from the Gene Expression Omnibus (GEO) database to identify co-expressed gene modules in OB and OP. These modules underwent Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interaction analysis to discover Hub genes. Machine learning refined the gene selection, with further validation using additional datasets. Single-cell analysis emphasized specific cell subpopulations, and enzyme-linked immunosorbent assay (ELISA), protein blotting, and cellular staining were used to investigate key genes.


The Bone & Joint Journal
Vol. 106-B, Issue 10 | Pages 1059 - 1066
1 Oct 2024
Konishi T Hamai S Tsushima H Kawahara S Akasaki Y Yamate S Ayukawa S Nakashima Y

Aims

The Coronal Plane Alignment of the Knee (CPAK) classification has been developed to predict individual variations in inherent knee alignment. The impact of preoperative and postoperative CPAK classification phenotype on the postoperative clinical outcomes of total knee arthroplasty (TKA) remains elusive. This study aimed to examine the effect of postoperative CPAK classification phenotypes (I to IX), and their pre- to postoperative changes on patient-reported outcome measures (PROMs).

Methods

A questionnaire was administered to 340 patients (422 knees) who underwent primary TKA for osteoarthritis (OA) between September 2013 and June 2019. A total of 231 patients (284 knees) responded. The ­Knee Society Score 2011 (KSS 2011), Knee injury and Osteoarthritis Outcome Score-12 (KOOS-12), and Forgotten Joint Score-12 (FJS-12) were used to assess clinical outcomes. Using preoperative and postoperative anteroposterior full-leg radiographs, the arithmetic hip-knee-ankle angle (aHKA) and joint line obliquity (JLO) were calculated and classified based on the CPAK classification. To investigate the impact on PROMs, multivariable regression analyses using stepwise selection were conducted, considering factors such as age at surgery, time since surgery, BMI, sex, implant use, postoperative aHKA classification, JLO classification, and changes in aHKA and JLO classifications from preoperative to postoperative.


The Bone & Joint Journal
Vol. 106-B, Issue 10 | Pages 1190 - 1196
1 Oct 2024
Gelfer Y McNee AE Harris JD Mavrotas J Deriu L Cashman J Wright J Kothari A

Aims

The aim of this study was to gain a consensus for best practice of the assessment and management of children with idiopathic toe walking (ITW) in order to provide a benchmark for practitioners and guide the best consistent care.

Methods

An established Delphi approach with predetermined steps and degree of agreement based on a standardized protocol was used to determine consensus. The steering group members and Delphi survey participants included members from the British Society of Children’s Orthopaedic Surgery (BSCOS) and the Association of Paediatric Chartered Physiotherapists (APCP). The statements included definition, assessment, treatment indications, nonoperative and operative interventions, and outcomes. Descriptive statistics were used for analysis of the Delphi survey results. The AGREE checklist was followed for reporting the results.


Bone & Joint Research
Vol. 13, Issue 9 | Pages 452 - 461
5 Sep 2024
Lee JY Lee HI Lee S Kim NH

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 levels in 156 patients who had undergone provocation discography. Significant predictors of clinical findings were identified by univariate and multivariate analyses. Loading conditions were applied in FEM simulations to mimic biomechanical effects on intervertebral discs, focusing on maximal displacement and intradiscal pressures, gauged through alterations in disc morphology and physical stress.


Aims

This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation.

Methods

In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload.


Bone & Joint Research
Vol. 13, Issue 8 | Pages 411 - 426
28 Aug 2024
Liu D Wang K Wang J Cao F Tao L

Aims

This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms.

Methods

We analyzed microarray data from the Gene Expression Omnibus (GEO) database using weighted gene co-expression network analysis (WGCNA), machine learning, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify common genetic factors between POMP and sarcopenia. Further validation was done via differential gene expression in a new cohort. Single-cell analysis identified high expression cell subsets, with mononuclear macrophages in osteoporosis and muscle stem cells in sarcopenia, among others. A competitive endogenous RNA network suggested regulatory elements for these genes.


Bone & Joint 360
Vol. 13, Issue 4 | Pages 23 - 26
2 Aug 2024

The August 2024 Wrist & Hand Roundup360 looks at: Methotrexate shows potential in reducing pain for hand osteoarthritis with synovitis; Circumferential casting versus plaster splinting in adult distal radius fractures: the CAST study findings; Surgery shows superior long-term success for Dupuytren contracture compared to needle fasciotomy and collagenase injection; Evolving trends in surgical management of wrist arthritis: a decade-long national analysis; Mid-term outcomes of three commonly used surgical reconstructions for scapholunate instability; SLAC and SNAC: what is the evidence for treatment?; Steroids for trapeziometacarpal osteoarthritis?; When is it safe to return to driving after distal radius fracture fixation? A prospective study.


The Bone & Joint Journal
Vol. 106-B, Issue 8 | Pages 775 - 782
1 Aug 2024
Wagner M Schaller L Endstrasser F Vavron P Braito M Schmaranzer E Schmaranzer F Brunner A

Aims

Hip arthroscopy has gained prominence as a primary surgical intervention for symptomatic femoroacetabular impingement (FAI). This study aimed to identify radiological features, and their combinations, that predict the outcome of hip arthroscopy for FAI.

Methods

A prognostic cross-sectional cohort study was conducted involving patients from a single centre who underwent hip arthroscopy between January 2013 and April 2021. Radiological metrics measured on conventional radiographs and magnetic resonance arthrography were systematically assessed. The study analyzed the relationship between these metrics and complication rates, revision rates, and patient-reported outcomes.


Bone & Joint Research
Vol. 13, Issue 7 | Pages 362 - 371
17 Jul 2024
Chang H Liu L Zhang Q Xu G Wang J Chen P Li C Guo X Yang Z Zhang F

Aims

The metabolic variations between the cartilage of osteoarthritis (OA) and Kashin-Beck disease (KBD) remain largely unknown. Our study aimed to address this by conducting a comparative analysis of the metabolic profiles present in the cartilage of KBD and OA.

Methods

Cartilage samples from patients with KBD (n = 10) and patients with OA (n = 10) were collected during total knee arthroplasty surgery. An untargeted metabolomics approach using liquid chromatography coupled with mass spectrometry (LC-MS) was conducted to investigate the metabolomics profiles of KBD and OA. LC-MS raw data files were converted into mzXML format and then processed by the XCMS, CAMERA, and metaX toolbox implemented with R software. The online Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to annotate the metabolites by matching the exact molecular mass data of samples with those from the database.


Bone & Joint Open
Vol. 5, Issue 6 | Pages 524 - 531
24 Jun 2024
Woldeyesus TA Gjertsen J Dalen I Meling T Behzadi M Harboe K Djuv A

Aims

To investigate if preoperative CT improves detection of unstable trochanteric hip fractures.

Methods

A single-centre prospective study was conducted. Patients aged 65 years or older with trochanteric hip fractures admitted to Stavanger University Hospital (Stavanger, Norway) were consecutively included from September 2020 to January 2022. Radiographs and CT images of the fractures were obtained, and surgeons made individual assessments of the fractures based on these. The assessment was conducted according to a systematic protocol including three classification systems (AO/Orthopaedic Trauma Association (OTA), Evans Jensen (EVJ), and Nakano) and questions addressing specific fracture patterns. An expert group provided a gold-standard assessment based on the CT images. Sensitivities and specificities of surgeons’ assessments were estimated and compared in regression models with correlations for the same patients. Intra- and inter-rater reliability were presented as Cohen’s kappa and Gwet’s agreement coefficient (AC1).


Bone & Joint 360
Vol. 13, Issue 3 | Pages 24 - 27
3 Jun 2024

The June 2024 Foot & Ankle Roundup360 looks at: First MTPJ fusion in young versus old patients; Minimally invasive calcaneum Zadek osteotomy and the effect of sequential burr passes; Comparison between Achilles tendon reinsertion and dorsal closing wedge calcaneal osteotomy for the treatment of insertional Achilles tendinopathy; Revision ankle arthroplasty – is it worthwhile?; Tibiotalocalcaneal arthrodesis or below-knee amputation – salvage or sacrifice?; Fusion or replacement for hallux rigidus?.


Bone & Joint Research
Vol. 13, Issue 4 | Pages 157 - 168
4 Apr 2024
Lin M Chen G Yu H Hsu P Lee C Cheng C Wu S Pan B Su B

Aims

Osteosarcoma is the most common primary bone malignancy among children and adolescents. We investigated whether benzamil, an amiloride analogue and sodium-calcium exchange blocker, may exhibit therapeutic potential for osteosarcoma in vitro.

Methods

MG63 and U2OS cells were treated with benzamil for 24 hours. Cell viability was evaluated with the MTS/PMS assay, colony formation assay, and flow cytometry (forward/side scatter). Chromosome condensation, the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, cleavage of poly-ADP ribose polymerase (PARP) and caspase-7, and FITC annexin V/PI double staining were monitored as indicators of apoptosis. Intracellular calcium was detected by flow cytometry with Fluo-4 AM. The phosphorylation and activation of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) were measured by western blot. The expression levels of X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), SOD1, and SOD2 were also assessed by western blot. Mitochondrial status was assessed with tetramethylrhodamine, ethyl ester (TMRE), and intracellular adenosine triphosphate (ATP) was measured with BioTracker ATP-Red Live Cell Dye. Total cellular integrin levels were evaluated by western blot, and the expression of cell surface integrins was assessed using fluorescent-labelled antibodies and flow cytometry.


Bone & Joint Research
Vol. 13, Issue 4 | Pages 137 - 148
1 Apr 2024
Lu Y Ho T Huang C Yeh S Chen S Tsao Y

Aims

Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA).

Methods

Mesenchymal stem/stromal cells (MSCs) were isolated from rat bone marrow (BM) and used to evaluate the impact of 29-mer on chondrogenic differentiation of BM-MSCs in culture. Knee OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) in the right knees (set to day 0). The 29-mer dissolved in 5% hyaluronic acid (HA) was intra-articularly injected into right knees at day 8 and 12 after MIA injection. Subsequently, the therapeutic effect of the 29-mer/HA on OA was evaluated by the Osteoarthritis Research Society International (OARSI) histopathological scoring system and changes in hind paw weight distribution, respectively. The regeneration of chondrocytes in damaged AC was detected by dual-immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and chondrogenic markers.


Bone & Joint Research
Vol. 13, Issue 3 | Pages 110 - 123
7 Mar 2024
Xu J Ruan Z Guo Z Hou L Wang G Zheng Z Zhang X Liu H Sun K Guo F

Aims

Osteoarthritis (OA) is the most common chronic pathema of human joints. The pathogenesis is complex, involving physiological and mechanical factors. In previous studies, we found that ferroptosis is intimately related to OA, while the role of Sat1 in chondrocyte ferroptosis and OA, as well as the underlying mechanism, remains unclear.

Methods

In this study, interleukin-1β (IL-1β) was used to simulate inflammation and Erastin was used to simulate ferroptosis in vitro. We used small interfering RNA (siRNA) to knock down the spermidine/spermine N1-acetyltransferase 1 (Sat1) and arachidonate 15-lipoxygenase (Alox15), and examined damage-associated events including inflammation, ferroptosis, and oxidative stress of chondrocytes. In addition, a destabilization of the medial meniscus (DMM) mouse model of OA induced by surgery was established to investigate the role of Sat1 inhibition in OA progression.


The Bone & Joint Journal
Vol. 106-B, Issue 3 Supple A | Pages 74 - 80
1 Mar 2024
Heckmann ND Plaskos C Wakelin EA Pierrepont JW Baré JV Shimmin AJ

Aims

Excessive posterior pelvic tilt (PT) may increase the risk of anterior instability after total hip arthroplasty (THA). The aim of this study was to investigate the changes in PT occurring from the preoperative supine to postoperative standing position following THA, and identify factors associated with significant changes in PT.

Methods

Supine PT was measured on preoperative CT scans and standing PT was measured on preoperative and one-year postoperative standing lateral radiographs in 933 patients who underwent primary THA. Negative values indicate posterior PT. Patients with > 13° of posterior PT from preoperative supine to postoperative standing (ΔPT ≤ -13°) radiographs, which corresponds to approximately a 10° increase in functional anteversion of the acetabular component, were compared with patients with less change (ΔPT > -13°). Logistic regression analysis was used to assess preoperative demographic and spinopelvic parameters predictive of PT changes of ≤ -13°. The area under receiver operating characteristic curve (AUC) determined the diagnostic accuracy of the predictive factors.


The Bone & Joint Journal
Vol. 106-B, Issue 3 Supple A | Pages 17 - 23
1 Mar 2024
LaValva SM LeBrun DG Canoles HG Ren R Padgett DE Su EP

Aims

Professional dancers represent a unique patient population in the setting of hip arthroplasty, given the high degree of hip strength and mobility required by their profession. We sought to determine the clinical outcomes and ability to return to professional dance after total hip arthroplasty (THA) or hip resurfacing arthroplasty (HRA).

Methods

Active professional dancers who underwent primary THA or HRA at a single institution with minimum one-year follow-up were included in the study. Primary outcomes included the rate of return to professional dance, three patient-reported outcome measures (PROMs) (modified Harris Hip Score (mHHS), Hip disability and Osteoarthritis Outcome Score for Joint Replacement (HOOS-JR), and Lower Extremity Activity Scale (LEAS)), and postoperative complications.


The Bone & Joint Journal
Vol. 106-B, Issue 2 | Pages 182 - 188
1 Feb 2024
Gallego JA Rotman D Watts AC

Aims

Acute and chronic injuries of the interosseus membrane can result in longitudinal instability of the forearm. Reconstruction of the central band of the interosseus membrane can help to restore biomechanical stability. Different methods have been used to reconstruct the central band, including tendon grafts, bone-ligament-bone grafts, and synthetic grafts. This Idea, Development, Exploration, Assessment, and Long-term (IDEAL) phase 1 study aims to review the clinical results of reconstruction using a synthetic braided cross-linked graft secured at either end with an Endobutton to restore the force balance between the bones of the forearm.

Methods

An independent retrospective review was conducted of a consecutive series of 21 patients with longitudinal instability injuries treated with anatomical central band reconstruction between February 2011 and July 2019. Patients with less than 12 months’ follow-up or who were treated acutely were excluded, leaving 18 patients in total. Preoperative clinical and radiological assessments were compared with prospectively gathered data using range of motion and the abbreviated version of the Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH) functional outcome score.


Bone & Joint Research
Vol. 13, Issue 1 | Pages 4 - 18
2 Jan 2024
Wang Y Wu Z Yan G Li S Zhang Y Li G Wu C

Aims

cAMP response element binding protein (CREB1) is involved in the progression of osteoarthritis (OA). However, available findings about the role of CREB1 in OA are inconsistent. 666-15 is a potent and selective CREB1 inhibitor, but its role in OA is unclear. This study aimed to investigate the precise role of CREB1 in OA, and whether 666-15 exerts an anti-OA effect.

Methods

CREB1 activity and expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) in cells and tissues were measured by immunoblotting and immunohistochemical (IHC) staining. The effect of 666-15 on chondrocyte viability and apoptosis was examined by cell counting kit-8 (CCK-8) assay, JC-10, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining. The effect of 666-15 on the microstructure of subchondral bone, and the synthesis and catabolism of cartilage, in anterior cruciate ligament transection mice were detected by micro-CT, safranin O and fast green (S/F), immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA).


The Bone & Joint Journal
Vol. 106-B, Issue 1 | Pages 38 - 45
1 Jan 2024
Leal J Mirza B Davies L Fletcher H Stokes J Cook JA Price A Beard DJ

Aims

The aim of this study was to estimate the incremental use of resources, costs, and quality of life outcomes associated with surgical reconstruction compared to rehabilitation for long-standing anterior cruciate ligament (ACL) injury in the NHS, and to estimate its cost-effectiveness.

Methods

A total of 316 patients were recruited and randomly assigned to either surgical reconstruction or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment). Healthcare resource use and health-related quality of life data (EuroQol five-dimension five-level health questionnaire) were collected in the trial at six, 12, and 18 months using self-reported questionnaires and medical records. Using intention-to-treat analysis, differences in costs, and quality-adjusted life years (QALYs) between treatment arms were estimated adjusting for baseline differences and following multiple imputation of missing data. The incremental cost-effectiveness ratio (ICER) was estimated as the difference in costs divided by the difference in QALYs between reconstruction and rehabilitation.


Bone & Joint Research
Vol. 12, Issue 12 | Pages 734 - 746
12 Dec 2023
Chen M Hu C Hsu Y Lin Y Chen K Ueng SWN Chang Y

Aims

Therapeutic agents that prevent chondrocyte loss, extracellular matrix (ECM) degradation, and osteoarthritis (OA) progression are required. The expression level of epidermal growth factor (EGF)-like repeats and discoidin I-like domains-containing protein 3 (EDIL3) in damaged human cartilage is significantly higher than in undamaged cartilage. However, the effect of EDIL3 on cartilage is still unknown.

Methods

We used human cartilage plugs (ex vivo) and mice with spontaneous OA (in vivo) to explore whether EDIL3 has a chondroprotective effect by altering OA-related indicators.


Bone & Joint Research
Vol. 12, Issue 12 | Pages 722 - 733
6 Dec 2023
Fu T Chen W Wang Y Chang C Lin T Wong C

Aims

Several artificial bone grafts have been developed but fail to achieve anticipated osteogenesis due to their insufficient neovascularization capacity and periosteum support. This study aimed to develop a vascularized bone-periosteum construct (VBPC) to provide better angiogenesis and osteogenesis for bone regeneration.

Methods

A total of 24 male New Zealand white rabbits were divided into four groups according to the experimental materials. Allogenic adipose-derived mesenchymal stem cells (AMSCs) were cultured and seeded evenly in the collagen/chitosan sheet to form cell sheet as periosteum. Simultaneously, allogenic AMSCs were seeded onto alginate beads and were cultured to differentiate to endothelial-like cells to form vascularized bone construct (VBC). The cell sheet was wrapped onto VBC to create a vascularized bone-periosteum construct (VBPC). Four different experimental materials – acellular construct, VBC, non-vascularized bone-periosteum construct, and VBPC – were then implanted in bilateral L4-L5 intertransverse space. At 12 weeks post-surgery, the bone-forming capacities were determined by CT, biomechanical testing, histology, and immunohistochemistry staining analyses.


Bone & Joint Open
Vol. 4, Issue 12 | Pages 932 - 941
6 Dec 2023
Oe K Iida H Otsuki Y Kobayashi F Sogawa S Nakamura T Saito T

Aims. Although there are various pelvic osteotomies for acetabular dysplasia of the hip, shelf operations offer effective and minimally invasive osteotomy. Our study aimed to assess outcomes following modified Spitzy shelf acetabuloplasty. Methods. Between November 2000 and December 2016, we retrospectively evaluated 144 consecutive hip procedures in 122 patients a minimum of five years after undergoing modified Spitzy shelf acetabuloplasty for acetabular dysplasia including osteoarthritis (OA). Our follow-up rate was 92%. The mean age at time of surgery was 37 years (13 to 58), with a mean follow-up of 11 years (5 to 21). Advanced OA (Tönnis grade ≥ 2) was present preoperatively in 16 hips (11%). The preoperative lateral centre-edge angle ranged from -28° to 25°. Survival was determined by Kaplan-Meier analysis, using conversions to total hip arthroplasty as the endpoint. Risk factors for joint space narrowing less than 2 mm were analyzed using a Cox proportional hazards model. Results. The mean Merle d'Aubigné clinical score improved from 11.6 points (6 to 17) preoperatively to 15.9 points (12 to 18) at the last follow-up. The survival rates were 95% (95% confidence interval (CI) 91 to 99) and 86% (95% CI 50 to 97) at ten and 15 years. Multivariate Cox regression identified three factors associated with radiological OA progression: age (hazard ratio (HR) 2.85, 95% CI 1.05 to 7.76; p = 0.0398), preoperative joint space (HR 2.41, 95% CI 1.35 to 4.29; p = 0.0029), and preoperative OA (HR 8.34, 95% CI 0.94 to 73.77; p = 0.0466). Conclusion. Modified Spitzy shelf acetabuloplasty is an effective joint-preserving surgery with a wide range of potential indications. Cite this article: Bone Jt Open 2023;4(12):932–941


Bone & Joint Open
Vol. 4, Issue 11 | Pages 873 - 880
17 Nov 2023
Swaby L Perry DC Walker K Hind D Mills A Jayasuriya R Totton N Desoysa L Chatters R Young B Sherratt F Latimer N Keetharuth A Kenison L Walters S Gardner A Ahuja S Campbell L Greenwood S Cole A

Aims

Scoliosis is a lateral curvature of the spine with associated rotation, often causing distress due to appearance. For some curves, there is good evidence to support the use of a spinal brace, worn for 20 to 24 hours a day to minimize the curve, making it as straight as possible during growth, preventing progression. Compliance can be poor due to appearance and comfort. A night-time brace, worn for eight to 12 hours, can achieve higher levels of curve correction while patients are supine, and could be preferable for patients, but evidence of efficacy is limited. This is the protocol for a randomized controlled trial of ‘full-time bracing’ versus ‘night-time bracing’ in adolescent idiopathic scoliosis (AIS).

Methods

UK paediatric spine clinics will recruit 780 participants aged ten to 15 years-old with AIS, Risser stage 0, 1, or 2, and curve size (Cobb angle) 20° to 40° with apex at or below T7. Patients are randomly allocated 1:1, to either full-time or night-time bracing. A qualitative sub-study will explore communication and experiences of families in terms of bracing and research. Patient and Public Involvement & Engagement informed study design and will assist with aspects of trial delivery and dissemination.


Bone & Joint Research
Vol. 12, Issue 11 | Pages 677 - 690
1 Nov 2023
Wang X Jiang W Pan K Tao L Zhu Y

Aims

Currently, the effect of drug treatment for osteoporosis is relatively poor, and the side effects are numerous and serious. Melatonin is a potential drug to improve bone mass in postmenopausal women. Unfortunately, the mechanism by which melatonin improves bone metabolism remains unclear. The aim of this study was to further investigate the potential mechanism of melatonin in the treatment of osteoporosis.

Methods

The effects of melatonin on mitochondrial apoptosis protein, bmal1 gene, and related pathway proteins of RAW264.7 (mouse mononuclear macrophage leukaemia cells) were analyzed by western blot. Cell Counting Kit-8 was used to evaluate the effect of melatonin on cell viability. Flow cytometry was used to evaluate the effect of melatonin on the apoptosis of RAW264.7 cells and mitochondrial membrane potential. A reactive oxygen species (ROS) detection kit was used to evaluate the level of ROS in osteoclast precursors. We used bmal1-small interfering RNAs (siRNAs) to downregulate the Bmal1 gene. We established a postmenopausal mouse model and verified the effect of melatonin on the bone mass of postmenopausal osteoporosis in mice via micro-CT. Bmal1 lentiviral activation particles were used to establish an in vitro model of overexpression of the bmal1 gene.


Bone & Joint Research
Vol. 12, Issue 10 | Pages 667 - 676
19 Oct 2023
Forteza-Genestra MA Antich-Rosselló M Ramis-Munar G Calvo J Gayà A Monjo M Ramis JM

Aims

Extracellular vesicles (EVs) are nanoparticles secreted by all cells, enriched in proteins, lipids, and nucleic acids related to cell-to-cell communication and vital components of cell-based therapies. Mesenchymal stromal cell (MSC)-derived EVs have been studied as an alternative for osteoarthritis (OA) treatment. However, their clinical translation is hindered by industrial and regulatory challenges. In contrast, platelet-derived EVs might reach clinics faster since platelet concentrates, such as platelet lysates (PL), are already used in therapeutics. Hence, we aimed to test the therapeutic potential of PL-derived extracellular vesicles (pEVs) as a new treatment for OA, which is a degenerative joint disease of articular cartilage and does not have any curative or regenerative treatment, by comparing its effects to those of human umbilical cord MSC-derived EVs (cEVs) on an ex vivo OA-induced model using human cartilage explants.

Methods

pEVs and cEVs were isolated by size exclusion chromatography (SEC) and physically characterized by nanoparticle tracking analysis (NTA), protein content, and purity. OA conditions were induced in human cartilage explants (10 ng/ml oncostatin M and 2 ng/ml tumour necrosis factor alpha (TNFα)) and treated with 1 × 109 particles of pEVs or cEVs for 14 days. Then, DNA, glycosaminoglycans (GAG), and collagen content were quantified, and a histological study was performed. EV uptake was monitored using PKH26 labelled EVs.


Bone & Joint Open
Vol. 4, Issue 9 | Pages 696 - 703
11 Sep 2023
Ormond MJ Clement ND Harder BG Farrow L Glester A

Aims

The principles of evidence-based medicine (EBM) are the foundation of modern medical practice. Surgeons are familiar with the commonly used statistical techniques to test hypotheses, summarize findings, and provide answers within a specified range of probability. Based on this knowledge, they are able to critically evaluate research before deciding whether or not to adopt the findings into practice. Recently, there has been an increased use of artificial intelligence (AI) to analyze information and derive findings in orthopaedic research. These techniques use a set of statistical tools that are increasingly complex and may be unfamiliar to the orthopaedic surgeon. It is unclear if this shift towards less familiar techniques is widely accepted in the orthopaedic community. This study aimed to provide an exploration of understanding and acceptance of AI use in research among orthopaedic surgeons.

Methods

Semi-structured in-depth interviews were carried out on a sample of 12 orthopaedic surgeons. Inductive thematic analysis was used to identify key themes.


Bone & Joint Research
Vol. 12, Issue 8 | Pages 504 - 511
23 Aug 2023
Wang C Liu S Chang C

Aims

This study aimed to establish the optimal fixation methods for calcaneal tuberosity avulsion fractures with different fragment thicknesses in a porcine model.

Methods

A total of 36 porcine calcanea were sawed to create simple avulsion fractures with three different fragment thicknesses (5, 10, and 15 mm). They were randomly fixed with either two suture anchors or one headless screw. Load-to-failure and cyclic loading tension tests were performed for the biomechanical analysis.


Aims

Astragalus polysaccharide (APS) participates in various processes, such as the enhancement of immunity and inhibition of tumours. APS can affect osteoporosis (OP) by regulating the osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs). This study was designed to elucidate the mechanism of APS in hBMSC proliferation and osteoblast differentiation.

Methods

Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting were performed to determine the expression of microRNA (miR)-760 and ankyrin repeat and FYVE domain containing 1 (ANKFY1) in OP tissues and hBMSCs. Cell viability was measured using the Cell Counting Kit-8 assay. The expression of cyclin D1 and osteogenic marker genes (osteocalcin (OCN), alkaline phosphatase (ALP), and runt-related transcription factor 2 (RUNX2)) was evaluated using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Mineral deposits were detected through Alizarin Red S staining. In addition, Western blotting was performed to detect the ANKFY1 protein levels following the regulation of miR-760. The relationship between miR-760 and ANKFY1 was determined using a luciferase reporter assay.


Bone & Joint 360
Vol. 12, Issue 4 | Pages 23 - 26
1 Aug 2023

The August 2023 Wrist & Hand Roundup360 looks at: Complications and patient-reported outcomes after trapeziectomy with a Weilby sling: a cohort study; Swelling, stiffness, and dysfunction following proximal interphalangeal joint sprains; Utility of preoperative MRI for assessing proximal fragment vascularity in scaphoid nonunion; Complications and outcomes of operative treatment for acute perilunate injuries: a systematic review; The position of the median nerve in relation to the palmaris longus tendon at the wrist: a study of 784 MR images; Basal fractures of the ulnar styloid? A randomized controlled trial; Proximal row carpectomy versus four-corner arthrodesis in SLAC and SNAC wrist; Managing cold intolerance after hand injury: a systematic review.


Bone & Joint Open
Vol. 4, Issue 7 | Pages 507 - 515
6 Jul 2023
Jørgensen PB Jakobsen SS Vainorius D Homilius M Hansen TB Stilling M

Aims

The Exeter short stem was designed for patients with Dorr type A femora and short-term results are promising. The aim of this study was to evaluate the minimum five-year stem migration pattern of Exeter short stems in comparison with Exeter standard stems.

Methods

In this case-control study, 25 patients (22 female) at mean age of 78 years (70 to 89) received cemented Exeter short stem (case group). Cases were selected based on Dorr type A femora and matched first by Dorr type A and then age to a control cohort of 21 patients (11 female) at mean age of 74 years (70 to 89) who received with cemented Exeter standard stems (control group). Preoperatively, all patients had primary hip osteoarthritis and no osteoporosis as confirmed by dual X-ray absorptiometry scanning. Patients were followed with radiostereometry for evaluation of stem migration (primary endpoint), evaluation of cement quality, and Oxford Hip Score. Measurements were taken preoperatively, and at three, 12, and 24 months and a minimum five-year follow-up.


Bone & Joint Open
Vol. 4, Issue 6 | Pages 408 - 415
1 Jun 2023
Ramkumar PN Shaikh HJF Woo JJ Haeberle HS Pang M Brooks PJ

Aims

The aims of the study were to report for a cohort aged younger than 40 years: 1) indications for HRA; 2) patient-reported outcomes in terms of the modified Harris Hip Score (HHS); 3) dislocation rate; and 4) revision rate.

Methods

This retrospective analysis identified 267 hips from 224 patients who underwent an hip resurfacing arthroplasty (HRA) from a single fellowship-trained surgeon using the direct lateral approach between 2007 and 2019. Inclusion criteria was minimum two-year follow-up, and age younger than 40 years. Patients were followed using a prospectively maintained institutional database.


Bone & Joint Open
Vol. 4, Issue 5 | Pages 315 - 328
5 May 2023
De Klerk TC Dounavi DM Hamilton DF Clement ND Kaliarntas KT

Aims

The aim of this study was to determine the effectiveness of home-based prehabilitation on pre- and postoperative outcomes in participants awaiting total knee (TKA) and hip arthroplasty (THA).

Methods

A systematic review with meta-analysis of randomized controlled trials (RCTs) of prehabilitation interventions for TKA and THA. MEDLINE, CINAHL, ProQuest, PubMed, Cochrane Library, and Google Scholar databases were searched from inception to October 2022. Evidence was assessed by the PEDro scale and the Cochrane risk-of-bias (ROB2) tool.


Aims

To systematically review the efficacy of split tendon transfer surgery on gait-related outcomes for children and adolescents with cerebral palsy (CP) and spastic equinovarus foot deformity.

Methods

Five databases (CENTRAL, CINAHL, PubMed, Embase, Web of Science) were systematically screened for studies investigating split tibialis anterior or split tibialis posterior tendon transfer for spastic equinovarus foot deformity, with gait-related outcomes (published pre-September 2022). Study quality and evidence were assessed using the Methodological Index for Non-Randomized Studies, the Risk of Bias In Non-Randomized Studies of Interventions, and the Grading of Recommendations Assessment, Development and Evaluation.


Bone & Joint Research
Vol. 12, Issue 4 | Pages 274 - 284
11 Apr 2023
Du X Jiang Z Fang G Liu R Wen X Wu Y Hu S Zhang Z

Aims

This study aimed to investigate the role and mechanism of meniscal cell lysate (MCL) in fibroblast-like synoviocytes (FLSs) and osteoarthritis (OA).

Methods

Meniscus and synovial tissue were collected from 14 patients with and without OA. MCL and FLS proteins were extracted and analyzed by liquid chromatography‒mass spectrometry (LC‒MS). The roles of MCL and adenine nucleotide translocase 3 (ANT3) in FLSs were examined by enzyme-linked immunosorbent assay (ELISA), flow cytometry, immunofluorescence, and transmission electron microscopy. Histological analysis was performed to determine ANT3 expression levels in a male mouse model.


Bone & Joint Open
Vol. 4, Issue 4 | Pages 226 - 233
1 Apr 2023
Moore AJ Wylde V Whitehouse MR Beswick AD Walsh NE Jameson C Blom AW

Aims

Periprosthetic hip-joint infection is a multifaceted and highly detrimental outcome for patients and clinicians. The incidence of prosthetic joint infection reported within two years of primary hip arthroplasty ranges from 0.8% to 2.1%. Costs of treatment are over five-times greater in people with periprosthetic hip joint infection than in those with no infection. Currently, there are no national evidence-based guidelines for treatment and management of this condition to guide clinical practice or to inform clinical study design. The aim of this study is to develop guidelines based on evidence from the six-year INFection and ORthopaedic Management (INFORM) research programme.

Methods

We used a consensus process consisting of an evidence review to generate items for the guidelines and online consensus questionnaire and virtual face-to-face consensus meeting to draft the guidelines.


Bone & Joint Research
Vol. 12, Issue 3 | Pages 219 - 230
10 Mar 2023
Wang L Li S Xiao H Zhang T Liu Y Hu J Xu D Lu H

Aims

It has been established that mechanical stimulation benefits tendon-bone (T-B) healing, and macrophage phenotype can be regulated by mechanical cues; moreover, the interaction between macrophages and mesenchymal stem cells (MSCs) plays a fundamental role in tissue repair. This study aimed to investigate the role of macrophage-mediated MSC chondrogenesis in load-induced T-B healing in depth.

Methods

C57BL/6 mice rotator cuff (RC) repair model was established to explore the effects of mechanical stimulation on macrophage polarization, transforming growth factor (TGF)-β1 generation, and MSC chondrogenesis within T-B enthesis by immunofluorescence and enzyme-linked immunosorbent assay (ELISA). Macrophage depletion was performed by clodronate liposomes, and T-B healing quality was evaluated by histology and biomechanics. In vitro, bone marrow-derived macrophages (BMDMs) were stretched with CELLOAD-300 load system and macrophage polarization was identified by flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR). MSC chondrogenic differentiation was measured by histochemical analysis and qRT-PCR. ELISA and qRT-PCR were performed to screen the candidate molecules that mediated the pro-chondrogenic function of mechanical stimulated BMDMs.


Bone & Joint Open
Vol. 4, Issue 3 | Pages 146 - 157
7 Mar 2023
Camilleri-Brennan J James S McDaid C Adamson J Jones K O'Carroll G Akhter Z Eltayeb M Sharma H

Aims

Chronic osteomyelitis (COM) of the lower limb in adults can be surgically managed by either limb reconstruction or amputation. This scoping review aims to map the outcomes used in studies surgically managing COM in order to aid future development of a core outcome set.

Methods

A total of 11 databases were searched. A subset of studies published between 1 October 2020 and 1 January 2011 from a larger review mapping research on limb reconstruction and limb amputation for the management of lower limb COM were eligible. All outcomes were extracted and recorded verbatim. Outcomes were grouped and categorized as per the revised Williamson and Clarke taxonomy.


Bone & Joint Research
Vol. 12, Issue 3 | Pages 189 - 198
7 Mar 2023
Ruiz-Fernández C Ait Eldjoudi D González-Rodríguez M Cordero Barreal A Farrag Y García-Caballero L Lago F Mobasheri A Sakai D Pino J Gualillo O

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 levels of relevant factors involved in inflammatory responses, by quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. We also studied the presence of mCRP in human AF and NP tissues by immunohistochemistry.


Bone & Joint Research
Vol. 12, Issue 2 | Pages 91 - 102
1 Feb 2023
Li Z Chen M Wang Z Fan Q Lin Z Tao X Wu J Liu Z Lin R Zhao C

Aims

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.

Methods

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.


Bone & Joint Research
Vol. 12, Issue 2 | Pages 121 - 132
1 Feb 2023
Mo H Wang Z He Z Wan J Lu R Wang C Chen A Cheng P

Aims

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.

Methods

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.


Bone & Joint Research
Vol. 12, Issue 1 | Pages 46 - 57
17 Jan 2023
Piñeiro-Ramil M Sanjurjo-Rodríguez C Rodríguez-Fernández S Hermida-Gómez T Blanco-García FJ Fuentes-Boquete I Vaamonde-García C Díaz-Prado S

Aims

After a few passages of in vitro culture, primary human articular chondrocytes undergo senescence and loss of their phenotype. Most of the available chondrocyte cell lines have been obtained from cartilage tissues different from diarthrodial joints, and their utility for osteoarthritis (OA) research is reduced. Thus, the goal of this research was the development of immortalized chondrocyte cell lines proceeded from the articular cartilage of patients with and without OA.

Methods

Using telomerase reverse transcriptase (hTERT) and SV40 large T antigen (SV40LT), we transduced primary OA articular chondrocytes. Proliferative capacity, degree of senescence, and chondrocyte surface antigen expression in transduced chondrocytes were evaluated. In addition, the capacity of transduced chondrocytes to synthesize a tissue similar to cartilage and to respond to interleukin (IL)-1β was assessed.


Bone & Joint Research
Vol. 12, Issue 1 | Pages 33 - 45
16 Jan 2023
Li B Ding T Chen H Li C Chen B Xu X Huang P Hu F Guo L

Aims

Circular RNA (circRNA) is involved in the regulation of articular cartilage degeneration induced by inflammatory factors or oxidative stress. In a previous study, we found that the expression of circStrn3 was significantly reduced in chondrocytes of osteoarthritis (OA) patients and OA mice. Therefore, the aim of this paper was to explore the role and mechanism of circStrn3 in osteoarthritis.

Methods

Minus RNA sequencing, fluorescence in situ hybridization, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of circStrn3 in human and mouse OA cartilage tissues and chondrocytes. Chondrocytes were then stimulated to secrete exosomal miR-9-5p by cyclic tensile strain. Intra-articular injection of exosomal miR-9-5p into the model induced by destabilized medial meniscus (DMM) surgery was conducted to alleviate OA progression.


Bone & Joint Research
Vol. 12, Issue 1 | Pages 9 - 21
9 Jan 2023
Lu C Ho C Chen S Liu Z Chou PP Ho M Tien Y

Aims

The effects of remnant preservation on the anterior cruciate ligament (ACL) and its relationship with the tendon graft remain unclear. We hypothesized that the co-culture of remnant cells and bone marrow stromal cells (BMSCs) decreases apoptosis and enhances the activity of the hamstring tendons and tenocytes, thus aiding ACL reconstruction.

Methods

The ACL remnant, bone marrow, and hamstring tendons were surgically harvested from rabbits. The apoptosis rate, cell proliferation, and expression of types I and III collagen, transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), and tenogenic genes (scleraxis (SCX), tenascin C (TNC), and tenomodulin (TNMD)) of the hamstring tendons were compared between the co-culture medium (ACL remnant cells (ACLRCs) and BMSCs co-culture) and control medium (BMSCs-only culture). We also evaluated the apoptosis, cell proliferation, migration, and gene expression of hamstring tenocytes with exposure to co-culture and control media.


The Bone & Joint Journal
Vol. 104-B, Issue 12 | Pages 1334 - 1342
1 Dec 2022
Wilcox B Campbell RJ Low A Yeoh T

Aims

Rates of reverse total shoulder arthroplasty (rTSA) continue to grow. Glenoid bone loss and deformity remains a technical challenge to the surgeon and may reduce improvements in patients’ outcomes. However, there is no consensus as to the optimal surgical technique to best reconstruct these patients’ anatomy. This review aims to compare the outcomes of glenoid bone grafting versus augmented glenoid prostheses in the management of glenoid bone loss in primary reverse total shoulder arthroplasty.

Methods

This systematic review and meta-analysis evaluated study-level data in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We performed searches of Medline (Ovid), Embase (Ovid), and PubMed from their dates of inception to January 2022. From included studies, we analyzed data for preoperative and postoperative range of motion (ROM), patient-reported functional outcomes, and complication rates.


Bone & Joint Research
Vol. 11, Issue 12 | Pages 843 - 853
1 Dec 2022
Cai Y Huang C Chen X Chen Y Huang Z Zhang C Zhang W Fang X

Aims

This study aimed to explore the role of small colony variants (SCVs) of Staphylococcus aureus in intraosseous invasion and colonization in patients with periprosthetic joint infection (PJI).

Methods

A PJI diagnosis was made according to the MusculoSkeletal Infection Society (MSIS) for PJI. Bone and tissue samples were collected intraoperatively and the intracellular invasion and intraosseous colonization were detected. Transcriptomics of PJI samples were analyzed and verified by polymerase chain reaction (PCR).


Bone & Joint Research
Vol. 11, Issue 12 | Pages 862 - 872
1 Dec 2022
Wang M Tan G Jiang H Liu A Wu R Li J Sun Z Lv Z Sun W Shi D

Aims

Osteoarthritis (OA) is a common degenerative joint disease worldwide, which is characterized by articular cartilage lesions. With more understanding of the disease, OA is considered to be a disorder of the whole joint. However, molecular communication within and between tissues during the disease process is still unclear. In this study, we used transcriptome data to reveal crosstalk between different tissues in OA.

Methods

We used four groups of transcription profiles acquired from the Gene Expression Omnibus database, including articular cartilage, meniscus, synovium, and subchondral bone, to screen differentially expressed genes during OA. Potential crosstalk between tissues was depicted by ligand-receptor pairs.


Aims

To test the hypothesis that reseeded anterior cruciate ligament (ACL)-derived cells have a better ability to survive and integrate into tendon extracellular matrix (ECM) and accelerate the ligamentization process, compared to adipose-derived mesenchymal stem cells (ADMSCs).

Methods

Acellularized tibialis allograft tendons were used. Tendons were randomly reseeded with ACL-derived cells or ADMSCs. ACL-derived cells were harvested and isolated from remnants of ruptured ACLs during reconstruction surgery and cultured at passage three. Cell suspensions (200 µl) containing 2 × 106 ACL-derived cells or ADMSCs were prepared for the purpose of reseeding. At days 1, 3, and 7 post-reseeding, graft composites were assessed for repopulation with histological and immunohistochemical analysis. Matrix protein contents and gene expression levels were analyzed.


Bone & Joint Research
Vol. 11, Issue 10 | Pages 700 - 714
4 Oct 2022
Li J Cheung W Chow SK Ip M Leung SYS Wong RMY

Aims

Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models.

Methods

Literature research was performed on PubMed and Embase databases. Keywords used for search criteria were “bone AND biofilm”. Information on the species of the animal model, bacterial strain, evaluation of biofilm and bone infection, complications, key findings on observations, prevention, and treatment of biofilm were extracted.


Bone & Joint Research
Vol. 11, Issue 10 | Pages 723 - 738
4 Oct 2022
Liu Z Shen P Lu C Chou S Tien Y

Aims

Autologous chondrocyte implantation (ACI) is a promising treatment for articular cartilage degeneration and injury; however, it requires a large number of human hyaline chondrocytes, which often undergo dedifferentiation during in vitro expansion. This study aimed to investigate the effect of suramin on chondrocyte differentiation and its underlying mechanism.

Methods

Porcine chondrocytes were treated with vehicle or various doses of suramin. The expression of collagen, type II, alpha 1 (COL2A1), aggrecan (ACAN); COL1A1; COL10A1; SRY-box transcription factor 9 (SOX9); nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX); interleukin (IL)-1β; tumour necrosis factor alpha (TNFα); IL-8; and matrix metallopeptidase 13 (MMP-13) in chondrocytes at both messenger RNA (mRNA) and protein levels was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot. In addition, the supplementation of suramin to redifferentiation medium for the culture of expanded chondrocytes in 3D pellets was evaluated. Glycosaminoglycan (GAG) and collagen production were evaluated by biochemical analyses and immunofluorescence, as well as by immunohistochemistry. The expression of reactive oxygen species (ROS) and NOX activity were assessed by luciferase reporter gene assay, immunofluorescence analysis, and flow cytometry. Mutagenesis analysis, Alcian blue staining, reverse transcriptase polymerase chain reaction (RT-PCR), and western blot assay were used to determine whether p67phox was involved in suramin-enhanced chondrocyte phenotype maintenance.