Estrogen downregulates TAK1 expression in human fibroblast-like synoviocytes and in a rheumatoid arthritis model.

Abstract

Transforming growth factor β-activated kinase-1 (TAK1), a member of the mitogen-activated protein kinase family, plays a key role in the pathogenesis and progression of rheumatoid arthritis (RA). Estrogen has been previously reported to delay arthritis progression. However, the exact association between TAK1 and estrogen remains elusive. The present study demonstrated that TAK1 was upregulated in synoviocytes of patients with RA compared with patients with osteoarthritis and healthy controls. In addition, TAK1 was also expressed in cultured fibroblast-like synoviocytes (FLS), and its levels decreased significantly in 17β-estradiol (E2)-treated cells in a dose-dependent manner. Furthermore, administration of E2 significantly decreased TAK1 expression and attenuated the development of collagen-induced arthritis (CIA). Taken together, the findings of the present study suggested that E2 mediates a decrease of TAK1 in both FLS and CIA, which subsequently results in a suppression of the pathological process of CIA. Therefore, estrogen may serve as a potential therapeutic agent for the treatment of RA by targeting TAK1.