Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial inflammation and joint destruction. Bone marrow mesenchymal stem cells (BMSCs) have shown therapeutic potential in RA, but the underlying mechanisms remain poorly understood. Objectives: To investigate the effects of BMSCs on human RA fibroblast-like synovial MH7A cells and complete Freund's adjuvant (CFA)-induced arthritis in rats and to explore the involvement of the JAK/STAT and TLR-4/NF-?B signaling pathways. Methods: BMSCs were isolated and co-cultured with MH7A cells. CFA-induced arthritis rat models were established. MH7A cell viability, inflammatory cytokine levels, paw withdrawal thermal latency (PWTL), gait parameters and the expression of JAK/STAT and TLR-4/NF-?B pathway-related genes and proteins were assessed. Results: In-vitro, BMSC co-culture significantly inhibited MH7A cell viability and reduced TNF-?, IL-6 and IL-8 levels. BMSC treatment also downregulated the expression of JAK2, p-JAK2, STAT3, p-STAT3, TLR4, P65 and p-P65 in MH7A cells. In-vivo, BMSC administration improved PWTL and gait parameters, reduced serum inflammatory cytokine levels and suppressed the expression of JAK/STAT and TLR-4/NF-?B pathway components in synovial tissues of CFA-induced arthritic rats. Conclusion: BMSCs alleviate RA by inhibiting inflammatory responses in vitro and in vivo and the underlying mechanism may involve blockade of the JAK/STAT and TLR-4/NF-?B signaling pathways.