Aims. Mendelian randomization (MR) is considered to overcome the bias of observational studies, but there is no current meta-analysis of MR studies on rheumatoid arthritis (RA). The purpose of this study was to summarize the relationship between potential pathogenic factors and RA risk based on existing MR studies. Methods. PubMed, Web of Science, and Embase were searched for MR studies on influencing factors in relation to RA up to October 2022. Meta-analyses of MR studies assessing correlations between various potential pathogenic factors and RA were conducted. Random-effect and fixed-effect models were used to synthesize the odds ratios of various pathogenic factors and RA. The quality of the study was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology using Mendelian Randomization (STROBE-MR) guidelines. Results. A total of 517 potentially relevant articles were screened, 35 studies were included in the systematic review, and 19 studies were eligible to be included in the meta-analysis. Pooled estimates of 19 included studies (causality between 15 different risk factors and RA) revealed that obesity, smoking, coffee intake, lower education attainment, and Graves’ disease (GD) were related to the increased risk of RA. In contrast, the causality contribution from serum mineral levels (calcium, iron, copper, zinc, magnesium, selenium), alcohol intake, and chronic periodontitis to RA is not significant. Conclusion. Obesity, smoking, education attainment, and GD have real causal effects on the occurrence and development of RA. These results may provide insights into the genetic susceptibility and potential biological pathways of RA. Cite this article: Bone Joint Res 2023;12(9):601–614

Aims. Deciphering the genetic relationships between major depressive disorder (MDD) and osteoarthritis (OA) may facilitate an understanding of their biological mechanisms, as well as inform more effective treatment regimens. We aim to investigate the mechanisms underlying relationships between MDD and OA in the context of common genetic variations. Methods. Linkage disequilibrium score regression was used to test the genetic correlation between MDD and OA. Polygenic analysis was performed to estimate shared genetic variations between the two diseases. Two-sample bidirectional Mendelian randomization analysis was used to investigate causal relationships between MDD and OA. Genomic loci shared between MDD and OA were identified using cross-trait meta-analysis. Fine-mapping of transcriptome-wide associations was used to prioritize putatively causal genes for the two diseases. Results. MDD has a significant genetic correlation with OA (r. g. = 0.29) and the two diseases share a considerable proportion of causal variants. Mendelian randomization analysis indicates that genetic liability to MDD has a causal effect on OA (b. xy. = 0.24) and genetic liability to OA conferred a causal effect on MDD (b. xy. = 0.20). Cross-trait meta-analyses identified 29 shared genomic loci between MDD and OA. Together with fine-mapping of transcriptome-wide association signals, our results suggest that Estrogen Receptor 1 (ESR1), SRY-Box Transcription Factor 5 (SOX5), and Glutathione Peroxidase 1 (GPX1) may have therapeutic implications for both MDD and OA. Conclusion. The study reveals substantial shared genetic liability between MDD and OA, which may confer risk for one another. Our findings provide a novel insight into phenotypic relationships between MDD and OA. Cite this article: Bone Joint Res 2022;11(1):12–22

Aims. Staphylococcus aureus is a major cause of septic arthritis, and in vitro studies suggest α haemolysin (Hla) is responsible for chondrocyte death. We used an in vivo murine joint model to compare inoculation with wild type S. aureus 8325-4 with a Hla-deficient strain DU1090 on chondrocyte viability, tissue histology, and joint biomechanics. The aim was to compare the actions of S. aureus Hla alone with those of the animal’s immune response to infection. Methods. Adult male C57Bl/6 mice (n = 75) were randomized into three groups to receive 1.0 to 1.4 × 10. 7. colony-forming units (CFUs)/ml of 8325-4, DU1090, or saline into the right stifle joint. Chondrocyte death was assessed by confocal microscopy. Histological changes to inoculated joints were graded for inflammatory responses along with gait, weight changes, and limb swelling. Results. Chondrocyte death was greater with 8325-4 (96.2% (SD 5.5%); p < 0.001) than DU1090 (28.9% (SD 16.0%); p = 0.009) and both were higher than controls (3.8% (SD 1.2%)). Histology revealed cartilage/bone damage with 8325-4 or DU1090 compared to controls (p = 0.010). Both infected groups lost weight (p = 0.006 for both) and experienced limb swelling (p = 0.043 and p = 0.018, respectively). Joints inoculated with bacteria showed significant alterations in gait cycle with a decreased stance phase, increased swing phase, and a corresponding decrease in swing speed. Conclusion. Murine joints inoculated with Hla-producing 8325-4 experienced significantly more chondrocyte death than those with DU1090, which lack the toxin. This was despite similar immune responses, indicating that Hla was the major cause of chondrocyte death. Hla-deficient DU1090 also elevated chondrocyte death compared to controls, suggesting a smaller additional deleterious role of the immune system on cartilage. Cite this article: Bone Joint Res 2022;11(9):669–678

Aims. The aim of this study was to explore the genetic correlation and causal relationship between blood plasma proteins and rheumatoid arthritis (RA). Methods. Based on the genome-wide association studies (GWAS) summary statistics of RA from European descent and the GWAS summary datasets of 3,622 plasma proteins, we explored the relationship between RA and plasma proteins from three aspects. First, linkage disequilibrium score regression (LD score regression) was applied to detect the genetic correlation between RA and plasma proteins. Mendelian randomization (MR) analysis was then used to evaluate the causal association between RA and plasma proteins. Finally, GEO2R was used to screen the differentially expressed genes (DEGs) between patients with RA and healthy controls. Results. We found that seven kinds of plasma proteins had genetic correlations with RA, such as Soluble Receptor for Advanced Glycation End Products (sRAGE) (correlation coefficient = 0.2582, p = 0.049), vesicle transport protein USE1 (correlation coefficient = 0.1337, p = 0.018), and spermatogenesis-associated protein 20 (correlation coefficient = 0.3706, p = 0.018). There was a significant causal relationship between sRAGE and RA. By comparing the genes encoding seven plasma proteins, we found that only USE1 was a DEG associated with RA. Conclusion. Our study identified a set of candidate plasma proteins that showed signals correlated with RA. Since the results of this study need further experimental verification, they should be interpreted with caution. However, we hope that this paper will provide new insights for the discovery of pathogenic genes and RA pathogenesis in the future. Cite this article: Bone Joint Res 2022;11(2):134–142

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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.

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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.

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

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To explore key stakeholder views around feasibility and acceptability of trials seeking to prevent post-traumatic osteoarthritis (PTOA) following knee injury, and provide guidance for next steps in PTOA trial design.

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To explore the synovial expression of mucin 1 (MUC1) and its role in rheumatoid arthritis (RA), as well as the possible downstream mechanisms.

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Osteoarthritis (OA) is a common degenerative joint disease characterized by chronic inflammatory articular cartilage degradation. Long noncoding RNAs (lncRNAs) have been previously indicated to play an important role in inflammation-related diseases. Herein, the current study set out to explore the involvement of lncRNA H19 in OA.

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Exosomes (exo) are involved in the progression of osteoarthritis (OA). This study aimed to investigate the function of dysfunctional chondrocyte-derived exo (DC-exo) on OA in rats and rat macrophages.

Osteoarthritis (OA) is a highly prevalent degenerative joint disorder characterized by joint pain and physical disability. Aberrant subchondral bone induces pathological changes and is a major source of pain in OA. In the subchondral bone, which is highly innervated, nerves have dual roles in pain sensation and bone homeostasis regulation. The interaction between peripheral nerves and target cells in the subchondral bone, and the interplay between the sensory and sympathetic nervous systems, allow peripheral nerves to regulate subchondral bone homeostasis. Alterations in peripheral innervation and local transmitters are closely related to changes in nociception and subchondral bone homeostasis, and affect the progression of OA. Recent literature has substantially expanded our understanding of the physiological and pathological distribution and function of specific subtypes of neurones in bone. This review summarizes the types and distribution of nerves detected in the tibial subchondral bone, their cellular and molecular interactions with bone cells that regulate subchondral bone homeostasis, and their role in OA pain. A comprehensive understanding and further investigation of the functions of peripheral innervation in the subchondral bone will help to develop novel therapeutic approaches to effectively prevent OA, and alleviate OA pain.

Cite this article: Bone Joint Res 2022;11(7):439–452.

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Post-traumatic osteoarthritis (PTOA) is a subset of osteoarthritis (OA). The gut microbiome is shown to be involved in OA. However, the effect of exercise on gut microbiome in PTOA remains elusive.

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Osteoarthritis (OA) is the most prevalent systemic musculoskeletal disorder, characterized by articular cartilage degeneration and subchondral bone (SCB) sclerosis. Here, we sought to examine the contribution of accelerated growth to OA development using a murine model of excessive longitudinal growth. Suppressor of cytokine signalling 2 (SOCS2) is a negative regulator of growth hormone (GH) signalling, thus mice deficient in SOCS2 (Socs2^-/-) display accelerated bone growth.

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Minimally manipulated cells, such as autologous bone marrow concentrates (BMC), have been investigated in orthopaedics as both a primary therapeutic and augmentation to existing restoration procedures. However, the efficacy of BMC in combination with tissue engineering is still unclear. In this study, we aimed to determine whether the addition of BMC to an osteochondral scaffold is safe and can improve the repair of large osteochondral defects when compared to the scaffold alone.

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This study investigates the effects of intra-articular injection of adipose-derived mesenchymal stem cells (AdMSCs) and platelet-rich plasma (PRP) on lameness, pain, and quality of life in osteoarthritic canine patients.

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Poly (ADP-ribose) polymerase (PARP) inhibitor has been reported to attenuate inflammatory response in rat models of inflammation. This study was designed to investigate the effect of PARP signalling in osteoarthritis (OA) cartilage inflammatory response in an OA rat model.

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This study aimed to investigate whether human umbilical cord mesenchymal stem cells (UC-MSCs) can prevent articular cartilage degradation and explore the underlying mechanisms in a rat osteoarthritis (OA) model induced by monosodium iodoacetate (MIA).

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Osteoarthritis (OA) is a disabling joint disorder and mechanical loading is an important pathogenesis. This study aims to investigate the benefits of less mechanical loading created by intermittent tail suspension for knee OA.

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The study aimed to determine whether the microRNA miR21-5p (MiR21) mediates temporomandibular joint osteoarthritis (TMJ-OA) by targeting growth differentiation factor 5 (Gdf5).