Role of nuclear factor of activated T cells 1 in the pathogenesis of osteoarthritis

Osteoarthritis (OA) is the most common form of joint disease in middle-aged individuals and the elderly. Previous studies have shown that the overexpression of matrix-degrading proteinases and proinflammatory cytokines is associated with the degradation of osteoarthritic cartilage. However, the transcription factors involved remain unclear. The present study aimed to determine the expression levels of nuclear factor of activated T cells 1 (NFAT1), interleukin-1 (IL-1) and tumor necrosis factor- (TNF-) in patients with OA, and to validate the role of NFAT1 in the pathogenesis of OA. The expression levels of NFAT1, IL-1 and TNF- in chondrocytes in the cartilage of patients with OA and healthy individuals were evaluated using western blot analysis. A luciferase reporter assay was performed to determine the activity of NFAT1 in primary human chondrocytes that were transfected with pNFAT1-luc plasmid and stimulated by IL-1. An enzyme-linked immunosorbent assay was performed to detect the levels of TNF-, matrix metalloproteinase (MMP)-1, MMP-3 and MMP-9 in the supernatant of cultured chondrocytes in which the NFAT1 was silenced. The expression levels of NFAT1, IL-1 and TNF- in the cartilage of patients with OA were higher than those of the controls. IL-1 induced the expression of NFAT1 in primary chondrocytes. The expression levels of TNF-, MMP-1, -3 and -9 promoted by IL-1 were decreased in NFAT1-silenced chondrocytes. In conclusion, NFAT1 may be important in the pathogenesis of OA and calcineurin-NFAT inhibitors may be potential effective agents for the treatment of OA.