Aims. 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. Methods. Six sets of gene expression profiles were obtained from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and multiple machine-learning algorithms were used to screen crucial genes in osteoarthritic cartilage, and genome enrichment and functional annotation analyses were used to decipher the related categories of gene function. Single-sample gene set enrichment analysis was performed to analyze immune cell infiltration. Correlation analysis was used to explore the relationship among the hub genes and immune cells, as well as markers related to articular cartilage degradation and bone mineralization. Results. A total of 46 genes were obtained from the intersection of significantly upregulated genes in osteoarthritic cartilage and the key module genes screened by WGCNA. Functional annotation analysis revealed that these genes were closely related to pathological responses associated with OA, such as inflammation and immunity. Four key dysregulated genes (cartilage acidic protein 1 (CRTAC1), iodothyronine deiodinase 2 (DIO2), angiopoietin-related protein 2 (ANGPTL2), and MAGE family member D1 (MAGED1)) were identified after using machine-learning algorithms. These genes had high diagnostic value in both the training cohort and external validation cohort (receiver operating characteristic > 0.8). The upregulated expression of these hub genes in osteoarthritic cartilage signified higher levels of immune infiltration as well as the expression of metalloproteinases and mineralization markers, suggesting harmful biological alterations and indicating that these hub genes play an important role in the pathogenesis of OA. A competing endogenous RNA network was constructed to reveal the underlying post-transcriptional regulatory mechanisms. Conclusion. The current study explores and validates a dysregulated key gene set in osteoarthritic cartilage that is capable of accurately diagnosing OA and characterizing the biological alterations in osteoarthritic cartilage; this may become a promising indicator in clinical decision-making. This study indicates that dysregulated key genes play an important role in the development and progression of OA, and may be potential therapeutic targets. Cite this article: Bone Joint Res 2024;13(2):66–82

Aims. Adenosine, lidocaine, and Mg. 2+. (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery. Methods. Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed. Results. Despite comparable knee function, ALM-treated males had reduced systemic inflammation, synovial fluid angiogenic and pro-inflammatory mediators, synovitis, and fat pad fibrotic changes, compared to controls. Within the ACL graft, ALM-treated males had increased expression of tissue repair markers, decreased inflammation, increased collagen organization, and improved graft-bone healing. In contrast to males, females had no evidence of persistent systemic inflammation. Compared to controls, ALM-treated females had improved knee extension, gait biomechanics, and elevated synovial macrophage inflammatory protein-1 alpha (MIP-1α). Within the ACL graft, ALM-treated females had decreased inflammation, increased collagen organization, and improved graft-bone healing. In articular cartilage of ALM-treated animals, matrix metalloproteinase (MMP)-13 expression was blunted in males, while in females repair markers were increased. Conclusion. At 28 days, ALM therapy reduces inflammation, augments tissue repair patterns, and improves joint function in a sex-specific manner. The study supports transition to human safety trials. Cite this article: Bone Joint Res 2024;13(6):279–293

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.

Aims

To map the Oxford Knee Score (OKS) and High Activity Arthroplasty Score (HAAS) items to a common scale, and to investigate the psychometric properties of this new scale for the measurement of knee health.

Objectives. Orthopaedic surgeons use stems in revision knee surgery to obtain stability when metaphyseal bone is missing. No consensus exists regarding stem size or method of fixation. This in vitro study investigated the influence of stem length and method of fixation on the pattern and level of relative motion at the bone–implant interface at a range of functional flexion angles. Methods. A custom test rig using differential variable reluctance transducers (DVRTs) was developed to record all translational and rotational motions at the bone–implant interface. Composite femurs were used. These were secured to permit variation in flexion angle from 0° to 90°. Cyclic loads were applied through a tibial component based on three peaks corresponding to 0°, 10° and 20° flexion from a normal walking cycle. Three different femoral components were investigated in this study for cementless and cemented interface conditions. Results. Relative motions were found to increase with flexion angle. Stemmed implants reduced relative motions in comparison to stemless implants for uncemented constructs. Relative motions for cemented implants were reduced to one-third of their equivalent uncemented constructs. Conclusions. Stems are not necessary for cemented implants when the metaphyseal bone is intact. Short cemented femoral stems confer as much stability as long uncemented stems