Infiltration Profile of Regulatory T Cells in Osteoarthritis-Related Pain and Disability.

Emerging evidence indicates that regulatory T cells (Treg) intervene in the inflammatory processes that drive osteoarthritis (OA). However, whether polarized Tregs affect clinical features of the disease in the short- or long-term, and if so, what their role in OA-related pain and functional disability really is, remains elusive. Thus, the aim of the current study was to characterize the infiltration profile of Tregs in systemic (peripheral blood) and joint-derived (synovial fluid and synovial membrane) samples from patients with knee OA in relation to OA-induced symptoms. To this end, Treg infiltration (CD4+CD25+/high CD127low/-) was analyzed in matched samples of peripheral blood (PB), synovial fluid (SF) and synovial membrane (SM) from a total of 47 patients undergoing elective knee arthroplasty using flow cytometry. At the same time, knee pain and function were assessed and correlated with Treg proportions in different compartments (PB, SF, SM). Interestingly, matched-pair analysis revealed significantly higher Treg proportions in joint-derived samples than in PB, which was mainly attributed to the high Treg frequency in SF. Moreover, we found significant associations between infiltrating Tregs and OA-related symptoms which indicate that lower Treg proportions-especially in the SM-are related to increased pain and functional disability in knee OA. In conclusion, this study highlights the importance of local cellular inflammatory processes in OA pathology. Intra-articular Treg infiltration might play an important role not only in OA pathogenesis but also in the development of OA-related symptoms.

Exploring Diagnostic Biomarkers and Comorbid Pathogenesis for Osteoarthritis and Metabolic Syndrome via Bioinformatics Approach.

BACKGROUND: Metabolic syndrome (MS) has grown in recognition to contribute to the pathogenesis of osteoarthritis (OA), which is the most prevalent arthritis characterized by joint dysfunction. However, the specific mechanism between OA and MS remains unclear. METHODS: The gene expression profiles and clinical information data of OA and MS were retrieved from the Gene Expression Omnibus (GEO) database. The genes in the key module of MS were identified by weighted gene co-expression network analysis (WGCNA), which intersected with the differentially expressed genes (DEGs) between control and MS samples to obtain hub genes for MS. The potential functions and pathways of hub genes were detected through the Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) analyses. The genes involved in the different KEGG pathways between the control and OA samples overlapped with the DEGs between the two groups via the Venn analysis to gain the hub genes for OA affected by MS (MOHGs). Additionally, the least absolute shrinkage and selection operator (LASSO) was performed on the MOHGs to establish a diagnostic model for each disease. RESULTS: A total of 61 hub genes for MS were identified that significantly enriched in platelet activation, complement and coagulation cascades, and hematopoietic cell lineage. Besides, 4 candidate genes (ELOVL7, F2RL3, GP9, and ITGA2B) were screened among the 6 MOHGs to construct a diagnostic model, showing good performance for distinguishing controls from patients with MS and OA. GSEA suggested that these diagnostic genes were closely associated with immune response, adipocytokine signaling, fatty acid metabolism, cell cycle, and platelet activation. CONCLUSION: Taken together, we identified 4 potential gene biomarkers for diagnosing MS and OA patients, providing a theoretical basis and reference for the diagnostics and treatment targets of MS and OA.

T Helper Cell Infiltration in Osteoarthritis-Related Knee Pain and Disability.

Despite the growing body of literature demonstrating a crucial role of T helper cell (Th) responses in the pathogenesis of osteoarthritis (OA), only few clinical studies have assessed interactions between Th cells and OA-related symptoms. Yet, the inclusion of clinical data in the interpretation of cellular analyses of Th cell infiltration is essential to reveal the mechanisms underlying the complex pathophysiology of OA pain and disability. Thus, the aim of the study was to analyze the infiltration pattern of Th cells in systemic (peripheral blood) and joint-derived (synovial membrane and fluid) samples from patients with knee OA in relation to OA-induced pain and disability. Therefore, radiographic OA severity, knee pain and function of 47 OA patients undergoing knee arthroplasty were evaluated prior to surgery. In parallel, samples of peripheral blood (PB), synovial membrane (SM) and synovial fluid (SF) were harvested and analyzed for different Th subsets using flow cytometry. According to surface marker expression Th cells (CD3+ CD4+ CD8-) were assigned to the Th subsets Th1 (CXCR3+, CCR5+), Th2 (CCR3+, CCR4+) and Th17 (CD161+, CCR6+). Interestingly, infiltration of the SM with all Th subtypes (Th1, Th2, Th17) significantly correlated with OA-induced disability. Most importantly, synovial CCR5+ and CCR3+ Th cell infiltration was associated with OA-related knee pain and disability. Furthermore, higher percentage rates of CXCR3+ Th cells in all tissue samples (PB, SM, SF) showed significant associations with OA severity. In contrast, increasing percentage rates of CD161+ Th cells in SM samples corresponded to a better functional outcome. In conclusion, the current study provides an extensive profile of the Th cell infiltration pattern in PB, SF and SM from patients with clinically relevant knee OA. Th cell infiltration of the SM might play a crucial role not only in the pathogenesis of OA but also in the development of OA-related knee pain and disability.