Myostatin Regulates Inflammatory Cytokine and Chemokine Expression, Rheumatoid Arthritis Synovial Fibroblast Invasion, and CD4+ Th Cell Transmigration

Résumé fourni par la source

Rheumatoid arthritis synovial fibroblasts (RASFs) play a pivotal role in joint destruction in RA. Myostatin (MSTN), a myokine, is highly expressed in the RA synovium; however, its role in the function of RASFs is unclear. We hypothesized that MSTN amplifies inflammatory cytokines/chemokines, promotes RASF invasion, and facilitates CD4+ Th cell transmigration. Immortalized MH7A cells (RASFs) and healthy synovial fibroblasts (HSFs) were treated with MSTN (0, 10, 20 ng/mL) for 0, 24, and 48 h. Cytokines (IL-8, IL-17, TNF-α, IL-6, IL-23, IFN-γ, IFN-β) and chemokines (CCL2, CCL20, CXCL13, CXCL1) were quantified by ELISA, RT-qPCR, and Western blotting. To evaluate MSTN regulation, cells were treated with pro-inflammatory mediators (TNF-α, IL-17, IFN-γ, IFN-β, CCL2, CXCL1). MSTN’s effects on Thy-1(CD90)+ RASF/HSF proliferation, RASF invasion, and CD4+ T-cell transmigration were assessed. Compared with HSFs, RASFs exhibited greater proliferative activity. MSTN significantly upregulated cytokines/chemokines, with CXCL1 showing the strongest induction in RASFs. IFN-γ and IL-17 robustly increased MSTN expression, indicating a feed-forward loop. MSTN did not alter Thy-1(CD90)+ fibroblast proliferation but significantly enhanced RASF invasion and CD4+ T-cell transmigration. Neutralizing CXCL1 or IL-17 reduced transmigration, with stronger inhibition via CXCL1. These findings offer new insights into the role of MSTN in RA pathogenesis and highlight its potential as a therapeutic target.

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