Abstract. Introduction. It is increasingly evident that synovium may play a larger role in the aetiology of osteoarthritis. We compared gene expression in whole tissue synovial biopsies from end-stage knee osteoarthritis and knee trauma patients with that of their paired explant cultures to determine how accurately cultured cells represent holistic synovial function. Methodology. Synovial tissue biopsies were taken from 16 arthroplasty patients and 8 tibial plateau fracture patients with no osteoarthritis. Pairs of whole tissue fragments were either immediately immersed in RNAlater Stabilisation Solution at 4o C before transfer to -80o C storage until RNA extraction; or weighed, minced and cultured at 500mg tissues/5ml media in a humidified incubator at 37oC, 5% CO2. After sub-culturing total RNA was extracted using RNAeasy Plus Mini Kit with gDNA removal. Following RT-PCR and quality assessment, cDNA was applied to Affymetrix Clariom D microarray gene chips. Bioinformatics analyses were performed. Results. PCA analysis illustrates the clear separation of expression array data from cultured cells compared with their parental whole tissues and no segregation between cells derived from osteoarthritic or trauma tissues. A differentially expressed gene heat map demonstrated the hierarchical independence of cultured cells from their paired sample parental tissues. The biological pathways enriched by these gene expression differences emphasise the activities of macrophages and lymphocytes lost from culture. Conclusion. Adherent synovial cells grown from different knee pathologies lose the expression patterns characteristic of their originating pathology. Interpretation of data needs caution as the cells are not representative of whole synovium

Abstract. Introduction. Articular cartilage degradation is a defining feature of osteoarthritis. Synovium is a reactive tissue with synovial villae, neoangiogenesis and intimal hyperplasia common to many joint pathologies. The consequences of cartilage debris in osteoarthritis impacting the synovial intima is not well understood. We analysed the immunohistology of synovium from 16 patients with osteoarthritis and 17 patients undergoing knee surgery for non-arthritic pathologies. This data was integrated with imaging and functional scores to correlate synovitis in osteoarthritis. Methodology. Formalin-fixed paraffin embedded synovial biopsy sections were cut in serial sequence and processed for routine staining (H&E or CD3, CD68, CD20, Vimentin, vWF and PCNA IHC) using standardised Dako monoclonal mouse anti-human antibodies. Digital images scanned at x20 were evaluated for fragments of cartilage and aggregates of inflammatory cells. Clinical data (gender, BMI, KL grade, WOMAC & SF-12 scores) was aligned with histopathological data. Results. Cartilage fragments were seen in the synovial intimal layer from end-stage osteoarthritis especially those with BMI<30kg/m2. Macrophages, T-cells and B-cells were identified surrounding cartilage inclusions. Inflammatory aggregates of T-cells, B-cells and macrophages were located peri-cartilage in the intima and peri-vascular in the sub-intimal layer of the synovium. Worse synovitis and function scores were significantly associated with both cartilage inclusions and inflammatory aggregates. X-ray features linked to longer duration of symptoms were associated with inflammatory aggregates. Conclusion. The histological features of the synovium clearly reflect deteriorating joint structures and compromised clinical function

Aims. Metal particles detached from metal-on-metal hip prostheses (MoM-THA) have been shown to cause inflammation and destruction of tissues. To further explore this, we investigated the histopathology (aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) score) and metal concentrations of the periprosthetic tissues obtained from patients who underwent revision knee arthroplasty. We also aimed to investigate whether accumulated metal debris was associated with ALVAL-type reactions in the synovium. Methods. Periprosthetic metal concentrations in the synovia and histopathological samples were analyzed from 230 patients from our institution from October 2016 to December 2019. An ordinal regression model was calculated to investigate the effect of the accumulated metals on the histopathological reaction of the synovia. Results. Median metal concentrations were as follows: cobalt: 0.69 μg/g (interquartile range (IQR) 0.10 to 6.10); chromium: 1.1 μg/g (IQR 0.27 to 4.10); and titanium: 1.6 μg/g (IQR 0.90 to 4.07). Moderate ALVAL scores were found in 30% (n = 39) of the revised knees. There were ten patients with an ALVAL score of 6 or more who were revised for suspected periprosthetic joint infection (PJI), aseptic loosening, or osteolysis. R2 varied between 0.269 and 0.369 for the ordinal regression models. The most important variables were model type, indication for revision, and cobalt and chromium in the ordinal regression models. Conclusion. We found that metal particles released from the knee prosthesis can accumulate in the periprosthetic tissues. Several patients revised for suspected culture-negative PJI had features of an ALVAL reaction, which is a novel finding. Therefore, ALVAL-type reactions can also be found around knee prostheses, but they are mostly mild and less common than those found around metal-on-metal prostheses. Cite this article: Bone Joint Res 2024;13(4):149–156

Abstract. Introduction. Synovitis impacts osteoarthritis symptomatology and progression. The transcription factors controlling synovial gene expression have not been described. This study analyses gene expression in synovium samples from 16 patients with osteoarthritis with 9 undergoing arthroscopic and 8 knee trauma surgery for non-arthritic pathologies. Methodology. Intra-operative synovial biopsies were immersed in RNAlater at 4oC before storage at -80oC. Total RNA was extracted using RNAeasy. After purification, RT-PCR and quality assessment, cDNA was applied to Affymetrix Clariom D microarray gene chips. Bioinformatics analyses were performed. Linear models were prepared in limma with gender and BMI factors incorporated sequentially for each pathology comparison, generating 12 models of probes differentially expressed at FDR p<0.05 and Bayes number, B>0. Data analysis of differently expressed genes utilized Ingenuity Pathway Analysis and Cytoscape with Cluego and Cytohubba plug-ins. Results. Amongst the 2084 genes with significantly differential expression (DEG), 135 had transcription regulator capabilities and 121 a nuclear location. IPA analysis of OATKR and arthroscopic tissue comparison DEG identified 12 nuclear transcription factors linked to 31 DEG whose encoded proteins located within cytoplasmic and cell membrane compartments. All 12 were significantly up-regulated and acting in pathways up-regulating transcription of DNA and RNA, cell survival and angiogenesis while down-regulating senescence and apoptosis. NFE2L2, integral to the TGF-beta signalling pathway, was identified as a bottleneck gene. Conclusion. This analysis indicates the complexity of synovial gene expression regulation and offers target genes and pathways for evaluation during osteoarthritis pathogenesis

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The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice.

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This study investigated the effects of transcatheter arterial embolization (TAE) on pain, function, and quality of life in people with early-stage symptomatic knee osteoarthritis (OA) compared to a sham procedure.

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This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA.

Lipoma arborescens is a rare intra-articular lesion, characterised by diffuse replacement of the subsynovial tissue by mature fat cells, producing prominent villous transformation of the synovium. The aetiology of this benign condition is unknown. We describe six cases involving the knee discussing the symptoms, diagnosis and treatment

Between 1989 and 1993 we implanted a matrix support prosthesis made of carbon fibre for the treatment of chronic painful articular defects of the patella in 27 patients. The mean period of follow-up was 33 months (11 to 54) with clinical and arthroscopic evaluation of the implant. Overall, there were four excellent, three good, seven fair and 13 poor results. Nine patients subsequently had a patellectomy for persistent pain at a mean of 27 months after surgery (14 to 47). The mean visual analogue pain scores in those who retained their patella were 7.6 before operation and 5.5 at the time of the latest follow-up. Patient satisfaction for the entire group was 41%. There appeared to be good incorporation of the prosthesis and a satisfactory ingrowth of fibrocartilage, but the poor results in 48% and low patient satisfaction discourage us from recommending the procedure for lesions of the articular cartilage of the patella. The consistent seeding of the joint with carbon-fibre debris and a histiocytic giant-cell reaction in the synovium are also a cause for concern

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Meniscal injuries are common and often induce knee pain requiring surgical intervention. To develop effective strategies for meniscus regeneration, we hypothesized that a minced meniscus embedded in an atelocollagen gel, a firm gel-like material, may enhance meniscus regeneration through cell migration and proliferation in the gel. Hence, the objective of this study was to investigate cell migration and proliferation in atelocollagen gels seeded with autologous meniscus fragments in vitro and examine the therapeutic potential of this combination in an in vivo rabbit model of massive meniscus defect.

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Proliferation, migration, and differentiation of anterior cruciate ligament (ACL) remnant and surrounding cells are fundamental processes for ACL reconstruction; however, the interaction between ACL remnant and surrounding cells is unclear. We hypothesized that ACL remnant cells preserve the capability to regulate the surrounding cells’ activity, collagen gene expression, and tenogenic differentiation. Moreover, extracorporeal shock wave (ESW) would not only promote activity of ACL remnant cells, but also enhance their paracrine regulation of surrounding cells.

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Mesenchymal stem cells (MSCs) have several properties that may support their use as an early treatment option for osteoarthritis (OA). This study investigated the role of multiple injections of allogeneic bone marrow-derived stem cells (BMSCs) to alleviate the progression of osteoarthritic changes in the various structures of the mature rabbit knee in an anterior cruciate ligament (ACL)-deficient OA model.

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Options for the treatment of intra-articular ligament injuries are limited, and insufficient ligament reconstruction can cause painful joint instability, loss of function, and progressive development of degenerative arthritis. This study aimed to assess the capability of a biologically enhanced matrix material for ligament reconstruction to withstand tensile forces within the joint and enhance ligament regeneration needed to regain joint function.

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The results of irrigation and debridement with component retention (IDCR) in the treatment of acutely infected total knee arthroplasties (TKAs) have been variable. The aim of this study was to assess the outcome after IDCR when combined with chronic antibiotic suppression. We also evaluated survivorship free from subsequent infection, removal of the components, and death, as well as the risk factors for failure.

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Patients with flexion instability after total knee arthroplasty (TKA) often present with a recurrent effusion, which may be a haemarthrosis. While the radiographic factors contributing to flexion instability have been elucidated, the clinical diagnosis remains challenging. Our aim, in this study, was to determine the mean white cell count and differential profile in pre-operative aspirations of synovial fluid in a consecutive series of patients undergoing revision TKA for flexion instability.

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Unicompartmental knee arthroplasty (UKA) has been successfully performed in the United States healthcare system on outpatients. Despite differences in healthcare structure and financial environment, we hypothesised that it would be feasible to replicate this success and perform UKA with safe day of surgery discharge within the NHS, in the United Kingdom. This has not been reported in any other United Kingdom centres.

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The Bereiter trochleoplasty has been used in our unit for 12 years to manage recurrent patellar instability in patients with severe trochlea dysplasia. The aim of this study was to document the outcome of a large consecutive cohort of patients who have undergone this operation.

Objectives

The purpose of this study was to compare the joint space width between one-leg and both-legs standing radiographs in order to diagnose a primary osteoarthritis of the knee.

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Approved by the Food and Drug Administration in 2004, the Phase III Oxford Medial Partial Knee is used to treat anteromedial osteoarthritis (AMOA) in patients with an intact anterior cruciate ligament. This unicompartmental knee arthroplasty (UKA) is relatively new in the United States, and therefore long-term American results are lacking.

Cartilage repair in terms of replacement, or regeneration of damaged or diseased articular cartilage with functional tissue, is the ‘holy grail’ of joint surgery. A wide spectrum of strategies for cartilage repair currently exists and several of these techniques have been reported to be associated with successful clinical outcomes for appropriately selected indications. However, based on respective advantages, disadvantages, and limitations, no single strategy, or even combination of strategies, provides surgeons with viable options for attaining successful long-term outcomes in the majority of patients. As such, development of novel techniques and optimisation of current techniques need to be, and are, the focus of a great deal of research from the basic science level to clinical trials. Translational research that bridges scientific discoveries to clinical application involves the use of animal models in order to assess safety and efficacy for regulatory approval for human use. This review article provides an overview of animal models for cartilage repair.

Cite this article: Bone Joint Res 2014;4:89–94.