Intrinsic chondrogenic transcriptional marker expression is preserved in rheumatoid arthritis synovial fibroblasts but is negatively associated with methotrexate dose

Objectives The intrinsic chondrogenic potential of synovial fibroblasts in rheumatoid arthritis remains controversial. We examined transcriptional chondrogenic marker expression in rheumatoid arthritis-derived fibroblast-like synoviocytes and explored associated clinical factors. Methods Synovial tissues were obtained from patients undergoing total knee arthroplasty. Analyses focused on patients younger than 70 years to reduce age-related confounding. Healthy synovial cells served as controls. Cells underwent pellet culture under chondrogenic stimulation, and type II collagen and aggrecan mRNA expression was quantified. Associations with clinical variables were assessed using correlation and exploratory multivariable analyses with adjustment for multiple testing. Results Type II collagen and aggrecan expression did not differ between rheumatoid arthritis-derived fibroblast-like synoviocytes and healthy controls. Higher methotrexate dose was significantly associated with reduced type II collagen expression, and this association remained significant after false discovery rate adjustment. Exploratory multivariable analyses demonstrated an association between methotrexate dose and type II collagen expression. Conclusions Transcriptional chondrogenic marker expression under standardized induction conditions was preserved in rheumatoid arthritis-derived fibroblast-like synoviocytes and was negatively associated with methotrexate dose. These findings support a more nuanced view of synovial fibroblast biology in rheumatoid arthritis, beyond a purely destructive phenotype.