BMP9 inhibits the proliferation and migration of fibroblast-like synoviocytes in rheumatoid arthritis via the PI3K/AKT signaling pathway.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease; its pathogenesis remains unclear. Fibroblast-like synoviocytes (FLSs) play a vital role in the pathogenesis of RA. BMP9, a member of the bone morphogenetic protein (BMP) family, has been reported to play a critical role in both normal physiological processes and the pathology of various diseases. In this study, we explored the function and underlying mechanisms of BMP9 in the proliferation and migration of RA FLSs. We found that BMP9 expression was significantly downregulated in the synovial tissues of RA patients, compared with those of OA patients; BMP9 expression was also low in adjuvant-induced arthritis (AA) samples. Additionally, inhibition of BMP9 expression by BMP9 siRNA increased the proliferation of AA FLSs, and the expression of c-Myc, Cyclin D1, MMP-2, and MMP-9, but not TIMP-1, in AA FLSs. However, AA FLSs transfected with the overexpression vector PEX-3-BMP9 showed reduced proliferation and expression of c-Myc, Cyclin D1, MMP-2, and MMP-9, but not TIMP-1. Further studies indicate that BMP9 may induce the activation of the PI3K/AKT signaling pathway. Thus, these data indicate that BMP9 may play a critical role in the proliferation and migration of FLSs through the activation of the AKT signaling pathway.