Aims. Osteoarthritis (OA) affecting the thumb carpometacarpal joint (CMCJ) is a common painful condition. In this study, we aimed to explore clinicians’ approach to management with a particular focus on the role of specific interventions that will inform the design of future clinical trials. Methods. We interviewed a purposive sample of 24 clinicians, consisting of 12 surgeons and 12 therapists (four occupational therapists and eight physiotherapists) who managed patients with CMCJ OA. This is a qualitative study using semi-structured, online interviews. Interviews were audio-recorded, transcribed verbatim, and analyzed using thematic analysis. Results. A total of 14 themes were developed, six of which were developed relating to the clinical management of CMCJ OA: 1) A flexible ‘ladder’ approach starting with conservative treatment first; 2) The malleable role of steroid injection; 3) Surgery as an invasive and risky last resort; 4) A shared and collaborative approach; 5) Treating the whole person; and 6) Severity of life impact influences treatment. The remaining eight themes were developed relating to clinical trial barriers and facilitators: 1) We need to embrace uncertainty; 2) You are not losing out by taking part; 3) It is difficult to be neutral about certain treatments; 4) Difficult to recruit to ‘no treatment’ ; 5) Difficult to recruit to a trial comparing no surgery to surgery; 6) Patients are keen to participate in research; 7) Burden on staff and participants; and 8) A enthusiasm for a variety of potential trial arms. Conclusion. Our findings contribute to a better understanding of how clinicians manage thumb CMCJ OA in their practice settings. Our study also provides useful insights informing the design of randomized clinical trials involving steroid injections and surgery in people with thumb CMCJ OA. Cite this article: Bone Jt Open 2022;3(4):321–331

Aims. Circular RNA (circRNA) S-phase cyclin A-associated protein in the endoplasmic reticulum (ER) (circSCAPER, ID: hsa_circ_0104595) has been found to be highly expressed in osteoarthritis (OA) patients and has been associated with the severity of OA. Hence, the role and mechanisms underlying circSCAPER in OA were investigated in this study. Methods. In vitro cultured human normal chondrocyte C28/I2 was exposed to interleukin (IL)-1β to mimic the microenvironment of OA. The expression of circSCAPER, microRNA (miR)-140-3p, and enhancer of zeste homolog 2 (EZH2) was detected using quantitative real-time polymerase chain reaction and Western blot assays. The extracellular matrix (ECM) degradation, proliferation, and apoptosis of chondrocytes were determined using Western blot, cell counting kit-8, and flow cytometry assays. Targeted relationships were predicted by bioinformatic analysis and verified using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. The levels of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway-related protein were detected using Western blot assays. Results. CircSCAPER was highly expressed in OA cartilage tissues and IL-1β-induced chondrocytes. Knockdown of circSCAPER reduced IL-1β-evoked ECM degradation, proliferation arrest, and apoptosis enhancement in chondrocytes. Mechanistically, circSCAPER directly bound to miR-140-3p, and miR-140-3p inhibition reversed the effects of circSCAPER knockdown on IL-1β-induced chondrocytes. miR-140-3p was verified to target EZH2, and overexpression of miR-140-3p protected chondrocytes against IL-1β-induced dysfunction via targeting EZH2. Additionally, we confirmed that circSCAPER could regulate EZH2 through sponging miR-140-3p, and the circSCAPER/miR-140-3p/EZH2 axis could activate the PI3K/AKT pathway. Conclusion. CircSCAPER promoted IL-1β-evoked ECM degradation, proliferation arrest, and apoptosis enhancement in chondrocytes via regulating miR-140-3p/EZH2 axis, which gained a new insight into the pathogenesis of OA. Cite this article: Bone Joint Res 2022;11(2):61–72

Cartilage neoangiogenesis holds a key role in the development of osteoarthritis (OA) by promoting cartilage degradation with proteoglycan loss, subchondral bone sclerosis, osteophyte formation and synovial hyperplasia. This study aimed to assess the in vivo efficacy of bevacizumab, an antibody against vascular endothelial growth factor (VEGF) in an OA animal model. 24 New Zealand white rabbits underwent anterior cruciate ligament transection in order to spontaneously develop knee OA. Animals were divided into four groups: one receiving a sham intraarticular knee injection (saline) and three groups treated with 5, 10, and 20 mg intraarticular bevacizumab injections. The biological effect of the antibody on cartilage and synovium was evaluated through histology and quantified with the Osteoarthritis Research Society International (OARSI) scores. Immunohistochemical analysis was conducted to investigate type 2 collagen, aggrecan, and matrix metalloproteinase 13 (MMP-13) expression in both cartilage and synovium. Intraarticular bevacizumab led to a significant reduction of cartilage degeneration and synovial OA alterations. Immunohistochemistry showed a significantly reduced MMP-13 expression in all experimental groups, with the one receiving 20 mg bevacizumab showing the lowest. Furthermore, the antibody showed to increment the production of aggrecan and type 2 collagen after administration of 5, 10, and 20 mg. The group treated with 20 mg showed the highest levels of type 2 collagen expression, while aggrecan content was even higher than in the healthy cartilage. Intraarticular bevacizumab has demonstrated to effectively arrest OA progression in our model, with 20 mg being the most efficacious dose. By inhibiting cartilage and synovial neoangiogenesis, bevacizumab may serve as a possible disease-modifying osteoarthritis drug (DMOAD) in the next future

Objectives. Sagittal alignment of the lumbosacral spine, and specifically pelvic incidence (PI), has been implicated in the development of spine pathology, but generally ignored with regards to diseases of the hip. We aimed to determine if increased PI is correlated with higher rates of hip osteoarthritis (HOA). The effect of PI on the development of knee osteoarthritis (KOA) was used as a negative control. Methods. We studied 400 well-preserved cadaveric skeletons ranging from 50 to 79 years of age at death. Each specimen’s OA of the hip and knee were graded using a previously described method. PI was measured from standardised lateral photographs of reconstructed pelvises. Multiple regression analysis was performed to determine the relationship between age and PI with HOA and KOA. Results. The mean age was 60.2 years (standard deviation (. sd. ) 8.1), and the mean PI was 46.7° (. sd. 10.7°). Multiple regression analysis demonstrated a significant correlation between increased PI and HOA (standardised beta = 0.103, p = 0.017). There was no correlation between PI and KOA (standardised beta = 0.003, p = 0.912). Conclusion. Higher PI in the younger individual may contribute to the development of HOA in later life. Cite this article: Dr J. J. Gebhart. Relationship between pelvic incidence and osteoarthritis of the hip. Bone Joint Res 2016;5:66–72. DOI: 10.1302/2046-3758.52.2000552

Introduction. Matrilin-3 is a member of the recently described matrilin family of extracellular matrix proteins containing von Willebrand factor A-like domains. The matrilin-3 subunit can form homotetramers as well as hetero-oligomers together with subunits of matrilin-1 (cartilage matrix protein). It has a restricted tissue distribution and is strongly expressed in growing skeletal tissues. Detailed information on expression and distribution of extracellular matrix proteins is important to understand cartilage function in health and in disease like osteoarthritis. Methods. Matrilin-3 expression was analysed on decalcified normal cartilage/bone sections (N = 5) and decalcified cartilage/ bone sections with minor (N= 10), moderate (N = 10), and severe osteoarthritic lesions (N = 10). Osteoarthritic changes were classified histomorphologically, using the grading system of Mankin. Matrilin-3 expression was investigated by immunohistochemistry, in situ hybridization, Western blot analysis, and quantitative PCR. For immunohistochemistry, a polyclonal antibody against matrilin-3 was used. For Western blot analysis, cartilage extracts were obtained from normal and osteoarthritic samples, partially purified, and separated in SDS poly-acrylamide gelelectrophoreses. After blotting onto nitro-cellulose, matrilin-3 was visualized by incubation with the polyclonal anti-matrilin-3 antibody and chemiluminescence detection. Matrilin-3 -mRNA expression was determined by in situ hybridization using a digoxigenin-labeled anti-sense probe. Results. Our results indicate that matrilin-3 is a mandatory component of mature articular cartilage with its expression being restricted to chondrocytes from the tangential zone and the upper middle cartilage zone. Osteoarthritic cartilage samples with only moderate morphological osteoarthritic destructions have elevated levels of matrilin-3 mRNA. In parallel, we found an increased deposition of matrilin-3 protein in the cartilage matrix. Matrilin-3 staining was diffusely distributed in the cartilage matrix, with no cellular staining being detectable. In cartilage samples with minor osteoarthritic lesions, matrilin-3 deposition was restricted to the middle zone and to the upper deep zone. A strong correlation was found between enhanced matrilin-3 gene and protein expression and the extent of tissue damage. Sections with severe osteoarthritic destruction showed the highest amount of matrilin-3 mRNA, strong signals in in situ hybridization, and prominent protein deposition in the middle and deep cartilage zone. Conclusion. We conclude that matrilin-3 is an integral component of human articular cartilage matrix and that the enhanced expression of matrilin-3 in osteoarthritis may be a cellular response to the modified microenvironment in the disease

Osteoarthritis, the most common degenerative joint disease, significantly impairs life quality and labor capability of patients. Synovial inflammation, initiated by HMGB1 (High mobility group box 1)-induced activation of macrophage, precedes other pathological changes. As an upstream regulator of NF-κB (nuclear factor-kappa B) and MAPK (mitogen-activated protein kinase) signaling pathway, TAK1 (TGF-β activated kinase 1) participates in macrophage activation, while its function in osteoarthritis remains unveiled. This study aims to investigate the role of TAK1 in the pathogenesis of osteoarthritis via both in vitro and in vivo approaches. We performed immunohistochemical staining for TAK1 in synovial tissue, both in osteoarthritis patients and healthy control. Besides, immunofluorescence staining for F4/80 as macrophage marker and TAK1 were conducted as well. TAK1 expression was examined in RAW264.7 macrophages stimulated by HMGB1 via qPCR (Quantitative polymerase chain reaction) and Western blotting, and the effect of TAK1 inhibitor (5z-7 oxozeaenol) on TNF-α production was evaluated by immunofluorescence staining. Further, we explored the influence of intra-articular shRNA (short hairpin RNA) targeting TAK1 on collagenase-induced osteoarthritis in mice. Immunohistochemical staining confirmed significant elevation of TAK1 in osteoarthritic synovium, and immunofluorescence staining suggested macrophages as predominant residence of TAK1. In HMGB1-stimulated RAW264.7 macrophages, TAK1 expression was up-regulated both in mRNA and protein level. Besides, TAK1 inhibitor significantly impairs the production of TNF-α by macrophages upon HMGB1 stimulation. Moreover, intra-articular injection of lentivirus loaded with shRNA targeting TAK1 (sh-TAK1) reduced peri-articular osteophyte formation in collagenase-induced osteoarthritis in mice. TAK1 exerts a potent role in the pathogenesis of osteoarthritis by mediating the activation of macrophages

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial membrane inflammation, osteophyte formation, and subchondral bone sclerosis. Pathological changes in cartilage and subchondral bone are the main processes in OA. In recent decades, many studies have demonstrated that activin-like kinase 3 (ALK3), a bone morphogenetic protein receptor, is essential for cartilage formation, osteogenesis, and postnatal skeletal development. Although the role of bone morphogenetic protein (BMP) signalling in articular cartilage and bone has been extensively studied, many new discoveries have been made in recent years around ALK3 targets in articular cartilage, subchondral bone, and the interaction between the two, broadening the original knowledge of the relationship between ALK3 and OA. In this review, we focus on the roles of ALK3 in OA, including cartilage and subchondral bone and related cells. It may be helpful to seek more efficient drugs or treatments for OA based on ALK3 signalling in future

Aims. Machine learning (ML), a branch of artificial intelligence that uses algorithms to learn from data and make predictions, offers a pathway towards more personalized and tailored surgical treatments. This approach is particularly relevant to prevalent joint diseases such as osteoarthritis (OA). In contrast to end-stage disease, where joint arthroplasty provides excellent results, early stages of OA currently lack effective therapies to halt or reverse progression. Accurate prediction of OA progression is crucial if timely interventions are to be developed, to enhance patient care and optimize the design of clinical trials. Methods. A systematic review was conducted in accordance with PRISMA guidelines. We searched MEDLINE and Embase on 5 May 2024 for studies utilizing ML to predict OA progression. Titles and abstracts were independently screened, followed by full-text reviews for studies that met the eligibility criteria. Key information was extracted and synthesized for analysis, including types of data (such as clinical, radiological, or biochemical), definitions of OA progression, ML algorithms, validation methods, and outcome measures. Results. Out of 1,160 studies initially identified, 39 were included. Most studies (85%) were published between 2020 and 2024, with 82% using publicly available datasets, primarily the Osteoarthritis Initiative. ML methods were predominantly supervised, with significant variability in the definitions of OA progression: most studies focused on structural changes (59%), while fewer addressed pain progression or both. Deep learning was used in 44% of studies, while automated ML was used in 5%. There was a lack of standardization in evaluation metrics and limited external validation. Interpretability was explored in 54% of studies, primarily using SHapley Additive exPlanations. Conclusion. Our systematic review demonstrates the feasibility of ML models in predicting OA progression, but also uncovers critical limitations that currently restrict their clinical applicability. Future priorities should include diversifying data sources, standardizing outcome measures, enforcing rigorous validation, and integrating more sophisticated algorithms. This paradigm shift from predictive modelling to actionable clinical tools has the potential to transform patient care and disease management in orthopaedic practice. Cite this article: Bone Joint J 2024;106-B(11):1216–1222

The biological understanding for the disease progression osteoarthritis (OA) has uncovered specific biomarkers from either synovial fluid, articular chondrocytes or synoviocytes that can be used to diagnose the disease. Examples of these biomarkers include interleukin-1β (IL-1β) or collagen II fragments (1, 2). In parallel, isolation of chondrocytes or bone marrow derived mesenchymal stromal cells (MSCs) has yielded cell-based strategies that have shown long- term beneficial effects in a specific cohort of patients, specifically in traumatic cartilage lesions (2). This latter finding shows that patient stratification of OA is an important tool to both match patients for a specific treatment and to develop novel therapies, especially disease modifying drugs. In order to create disease stage specific therapies, the use of next generation analysis tools such as RNAseq and metabolomics, has the potential to decipher specific cellular and molecular endotypes. Alongside greater understanding of the clinical phenotype (e.g. imaging, pain, co- morbidities), therapies can be designed to alleviate the symptoms of OA at specific points of the disease in patients. This talk will outline the current biological understanding of OA and discuss how patient stratification could assist in the design of innovative therapies for the disease. Acknowledgements: This presentation was supported by the COST action, CA21110 – Building an open European Network on Osteoarthritis Research (NetwOArk)

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. Results. EDIL3 protein prevented chondrocyte clustering and maintained chondrocyte number and SOX9 expression in the human cartilage plug. Administration of EDIL3 protein prevented OA progression in STR/ort mice by maintaining the number of chondrocytes in the hyaline cartilage and the number of matrix-producing chondrocytes (MPCs). It reduced the degradation of aggrecan, the expression of matrix metalloproteinase (MMP)-13, the Osteoarthritis Research Society International (OARSI) score, and bone remodelling. It increased the porosity of the subchondral bone plate. Administration of an EDIL3 antibody increased the number of matrix-non-producing chondrocytes (MNCs) in cartilage and exacerbated the serum concentrations of OA-related pro-inflammatory cytokines, including monocyte chemotactic protein-3 (MCP-3), RANTES, interleukin (IL)-17A, IL-22, and GROα. Administration of β1 and β3 integrin agonists (CD98 protein) increased the expression of SOX9 in OA mice. Hence, EDIL3 might activate β1 and β3 integrins for chondroprotection. EDIL3 may also protect cartilage by attenuating the expression of IL-1β-enhanced phosphokinase proteins in chondrocytes, especially glycogen synthase kinase 3 alpha/beta (GSK-3α/β) and phospholipase C gamma 1 (PLC-γ1). Conclusion. EDIL3 has a role in maintaining the cartilage ECM and inhibiting the development of OA, making it a potential therapeutic drug for OA. Cite this article: Bone Joint Res 2023;12(12):734–746

Osteoarthritis (OA) is mainly caused by ageing, strain, trauma, and congenital joint abnormalities, resulting in articular cartilage degeneration. During the pathogenesis of OA, the changes in subchondral bone (SB) are not only secondary manifestations of OA, but also an active part of the disease, and are closely associated with the severity of OA. In different stages of OA, there were microstructural changes in SB. Osteocytes, osteoblasts, and osteoclasts in SB are important in the pathogenesis of OA. The signal transduction mechanism in SB is necessary to maintain the balance of a stable phenotype, extracellular matrix (ECM) synthesis, and bone remodelling between articular cartilage and SB. An imbalance in signal transduction can lead to reduced cartilage quality and SB thickening, which leads to the progression of OA. By understanding changes in SB in OA, researchers are exploring drugs that can regulate these changes, which will help to provide new ideas for the treatment of OA. Cite this article: Bone Joint Res 2023;12(9):536–545

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. Results. Tensile strain could decrease the expression of circStrn3 in chondrocytes. CircStrn3 expression was significantly decreased in human and mouse OA cartilage tissues and chondrocytes. CircStrn3 could inhibit matrix metabolism of chondrocytes through competitively ‘sponging’ miRNA-9-5p targeting Kruppel-like factor 5 (KLF5), indicating that the decrease in circStrn3 might be a protective factor in mechanical instability-induced OA. The tensile strain stimulated chondrocytes to secrete exosomal miR-9-5p. Exosomes with high miR-9-5p expression from chondrocytes could inhibit osteoblast differentiation by targeting KLF5. Intra-articular injection of exosomal miR-9-5p alleviated the progression of OA induced by destabilized medial meniscus surgery in mice. Conclusion. Taken together, these results demonstrate that reduction of circStrn3 causes an increase in miR-9-5p, which acts as a protective factor in mechanical instability-induced OA, and provides a novel mechanism of communication among joint components and a potential application for the treatment of OA. Cite this article: Bone Joint Res 2023;12(1):33–45

There is some evidence to suggest that outcomes of THA in patients with minimal radiographic osteoarthritis may not be associated with predictable outcomes. The aim of this study was to:. Assess the outcome of patients with hip pain who underwent THA with no or minimal radiographic signs of osteoarthritis,. Identify patient comorbidities and multiplanar imaging findings which are predictive of outcome,. Compare the outcome in these patients to the expected outcome of THA in hip OA. A retrospective review of 107 hips (102 patients, 90F:12M, median age 40.6, IQR 35.1–45.8 years, range 18–73) were included for analysis. Plain radiographs were evaluated using the Tonnis grading scale of hip OA. Outcome measures were all-cause revision; iHOT12; EQ-5D; Oxford Hip Score; UCLA Activity Scale; and whether THA had resulted in the patient's hip pain and function being Better/Same/Worse. The median Oxford Hip Score was 33.3 (IQR 13.9, range 13–48), and 36/107 (33.6%) hips achieved an OHS≥42. There was no association between primary hip diagnosis and post-operative PROMs. A total of 91 of the 102 patients (89.2%, 93 hips) reported that their hip pain and function was Better than prior to THA and would have the surgery again, 7 patients (6.8%, 10 hips) felt the Same, and 4 patients (3.9%, 4 hips) felt Worse and would not have the surgery again. Younger patients undergoing total hip arthroplasty with no or minimal radiographic osteoarthritis had lower postoperative Oxford Hip Scores than the general population; though most felt symptomatically better and knowing what they know now, would have surgery again. Those with chronic pain syndrome or hypermobility were likely to benefit less. Those with subchondral cysts or joint space narrowing on CT imaging were more likely to achieve higher functional scores and satisfaction

Osteoarthritis (OA) of the equine distal interphalangeal joint (DIPJ) is a common cause of lameness. MicroRNAs (miRNAs) from biofluids such as plasma and synovial fluid make promising biomarker and therapeutic candidates. The objectives of this study are (1) Identify differentially expressed (DE) miRNAs in mild and severe equine DIPJ OA synovial fluid samples and (2) Determine the effects of DE miRNAs on equine chondrocytes in monolayer culture. Synovial fluid samples from five horses with mild and twelve horses with severe DIPJ OA were submitted for RNA-sequencing; OA diagnosis was made from MRI T2 mapping, macroscopic and histological evaluation. Transfection of equine chondrocytes (n=3) was performed using the Lipofectamine® RNAiMAX system with a negative control and a miR-92a mimic and inhibitor. qPCR was used to quantify target mRNA genes. RNA-seq showed two miRNAs (miR-16 and miR-92a) were significantly DE (p<0.05). Ingenuity Pathway Analysis (IPA) identified important downstream targets of miR-92a involved in the pathogenesis of osteoarthritis and so this miRNA was used to transfect equine chondrocytes from three donor horses diagnosed with OA. Transfection was successfully demonstrated by a 1000-20000 fold increase in miR-92a expression in the equine chondrocytes. There was a significant (p<0.05) increase in COMP, COL3A1 and Sox9 in the miR-92a mimic treatment and there was no difference in ADAMTS-5 expression between the miR-92 mimic and inhibitor treatment. RNA-seq demonstrated miR-92a was downregulated in severe OA synovial fluid samples which has not previously been reported in horses, however miR-92a is known to play a role in the pathogenesis of OA in other species. Over expression of miR-92a in equine chondrocytes led to significantly increased COMP and Sox9 expression, consistent with a chondrogenic phenotype which has been identified in human and murine chondrocytes

Osteoarthritis (OA) is the most common joint disease, affecting approximately 16% of the adult population worldwide. The chronic inflammation in the joint leads to the breakdown of cartilage, which leads to permanent pain and limitations in everyday life at an early stage of the disease. To date, there is no therapy that can interrupt the inflammatory state or reverse cartilage damage. The PROTO consortium (funded by the EU Horizon Europe program, Grant 101095635) aims to prevent the development of OA by correcting a pathological biomechanical pattern by a digital training intervention and to treat early stage OA with an innovative allogeneic cell therapy

Knee arthroscopy with debridement is commonly performed to treat osteoarthritis and degenerative meniscal tears in older adults; however robust evidence does not support sustained benefit from this procedure. Current Canadian guidelines advise against its use as first line treatment. Characterizing the use of this low value procedure will facilitate efforts to maximize quality of care, minimize harm and decrease healthcare costs. We sought to understand:. 1). the volume and variations of arthroscopic knee debridement across Canada. 2). The costs associated with potentially unnecessary arthroscopy. 3). The characteristics of surgeons performing knee arthroscopy in older adults. Data were derived from National Ambulatory Care Reporting System (NACRS), the Discharge Abstract Database (DAD) and the National Physician Database for years 2011-12 to 2019-20. The study included all elective knee arthroscopies (CCI codes 1.VG.80.DA,1.VG.80.FY and 1.VG.87.DA) performed in day surgery and acute care settings in 9 provinces and 3 territories of Canada. Quebec was not included in the analysis due to different reporting methods. We set a threshold of 60 years of age at which it would be highly unlikely that a patient would undergo arthroscopy to treat anything other than osteoarthritis or degenerative meniscal tear. Trends at national and provincial levels were analyzed using regression. Costs were estimated separately using the 2020 case mix groups (CMG) and comprehensive ambulatory care classification system (CACS) methodologies. Surgeons were classified by decade of graduation from medical school (1989 and prior, 1990-99, 2000-09 and 2010+) and categorized based on the proportion of their patient population who were above (“high proportion inappropriate”) or below (“low proportion inappropriate”) the overall national proportion of ≥ 60 years of age. The number of knee arthroscopies decreased by 37% (42,785 in 2011-12 to 27,034 in 2019-20) overall and 39% (11,103 in 2011-12 to 6,772 in 2019-20) in those 60 years and older (p 25% of patients 60 years and older. Fifty four percent of surgeons who graduated prior to 1989 were considered high proportion inappropriate, whereas only 30.1% of surgeons who graduated in 2010 or later were considered high proportion inappropriate (p < 0 .0001). Knee arthroscopy continues to be a common procedure in patients over 60 despite strong evidence for lack of benefit. Lower rates in this population in some provinces are encouraging for potential opportunity for improvement. Efforts at practice change should be targeted at surgeons in practice the longest. Canada spends over $12,000,000 per year on this procedure, decreasing its use could allow these resources to be directed to other areas of orthopaedics that provide higher value care

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. Results. The 29-mer promoted expansion and chondrogenic differentiation of BM-MSCs cultured in different defined media. MIA injection caused chondrocyte death throughout the AC, with cartilage degeneration thereafter. The 29-mer/HA treatment induced extensive chondrocyte regeneration in the damaged AC and suppressed MIA-induced synovitis, accompanied by the recovery of cartilage matrix. Pharmacological inhibitors of PEDF receptor (PEDFR) and signal transducer and activator of transcription 3 (STAT3) signalling substantially blocked the chondrogenic promoting activity of 29-mer on the cultured BM-MSCs and injured AC. Conclusion. The 29-mer/HA formulation effectively induces chondrocyte regeneration and formation of cartilage matrix in the damaged AC. Cite this article: Bone Joint Res 2024;13(4):137–148

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. Results. During OA, there were 626, 97, 1,060, and 2,330 differentially expressed genes in articular cartilage, meniscus, synovium, and subchondral bone, respectively. Gene Ontology enrichment revealed that these genes were enriched in extracellular matrix and structure organization, ossification, neutrophil degranulation, and activation at different degrees. Through ligand-receptor pairing and proteome of OA synovial fluid, we predicted ligand-receptor interactions and constructed a crosstalk atlas of the whole joint. Several interactions were reproduced by transwell experiment in chondrocytes and synovial cells, including TNC-NT5E, TNC-SDC4, FN1-ITGA5, and FN1-NT5E. After lipopolysaccharide (LPS) or interleukin (IL)-1β stimulation, the ligand expression of chondrocytes and synovial cells was upregulated, and corresponding receptors of co-culture cells were also upregulated. Conclusion. Each tissue displayed a different expression pattern in transcriptome, demonstrating their specific roles in OA. We highlighted tissue molecular crosstalk through ligand-receptor pairs in OA pathophysiology, and generated a crosstalk atlas. Strategies to interfere with these candidate ligands and receptors may help to discover molecular targets for future OA therapy. Cite this article: Bone Joint Res 2022;11(12):862–872

An intra-articular steroid injection can be a useful diagnostic tool in patients presenting with debilitating hip pain and radiographically mild osteoarthritis. The clinical and patient reported outcomes associated with patients who have radiographically mild osteoarthritis and undergo total hip arthroplasty (THA) remain poorly studied. Patients undergoing primary, elective THA at a single academic medical center by a fellowship-trained adult reconstruction surgeon between 2017–2023 were identified. Only those patients who underwent an intra-articular corticosteroid injection into the operative hip within one year of surgery were included. Patients were divided into two cohorts based on the severity of their osteoarthritis as determined by preoperative radiographs; those with Kellgren-Lawrence (KL) grade I-II arthritis were classified as “mild” whereas those with KL grade III-IV arthritis were classified as “severe”. Clinical and patient reported outcomes at final follow-up were compared between cohorts. The final cohorts included 25 and 224 patients with radiographically mild and severe osteoarthritis, respectively. There were no baseline differences in age, gender or time between intra-articular corticosteroid injection and THA between cohorts. There were no significant differences in the preoperative or postoperative HOOS JR values between patients with mild or severe arthritis (all p>0.05). There were no significant differences in the change in HOOS JR scores from the preoperative to final follow-up timepoints between cohorts. There were no significant differences in the percentage of patients who achieved the minimal clinically important difference (MCID) on the HOOS JR questionnaire between cohorts. Patients with radiographically mild osteoarthritis who feel relief of their hip pain following an intra-articular corticosteroid injection report similar preoperative debility and demonstrate similar improvements in patient reported outcome scores following THA compared to patients with radiographically severe osteoarthritis

Aims. To evaluate inducing osteoarthritis (OA) by surgical destabilization of the medial meniscus (DMM) in mice with and without a stereomicroscope. Methods. Based on sample size calculation, 70 male C57BL/6 mice were randomly assigned to three surgery groups: DMM aided by a stereomicroscope; DMM by naked eye; or sham surgery. The group information was blinded to researchers. Mice underwent static weightbearing, von Frey test, and gait analysis at two-week intervals from eight to 16 weeks after surgery. Histological grade of OA was determined with the Osteoarthritis Research Society International (OARSI) scoring system. Results. Surgical DMM with or without stereomicroscope led to decrease in the mean of weightbearing percentages (-20.64% vs -21.44%, p = 0.792) and paw withdrawal response thresholds (-21.35% vs -24.65%, p = 0.327) of the hind limbs. However, the coefficient of variation (CV) of weight-bearing percentages and paw withdrawal response thresholds in naked-eye group were significantly greater than that in the microscope group (19.82% vs 6.94%, p < 0.001; 21.85% vs 9.86%, p < 0.001). The gait analysis showed a similar pattern. Cartilage degeneration was observed in both DMM-surgery groups, evidenced by increased OARSI scores (summed score: 11.23 vs 11.43, p = 0.842), but the microscope group showed less variation in OARSI score than the naked-eye group (CV: 21.03% vs 32.44%; p = 0.032). Conclusion. Although surgical DMM aided by stereomicroscope is technically difficult, it produces a relatively more homogeneous OA model in terms of the discrete degree of pain behaviours and histopathological grading when compared with surgical DMM without stereomicroscope. Cite this article: Bone Joint Res 2022;11(8):518–527