The roles of synovial hyperplasia, angiogenesis and osteoclastogenesis in the protective effect of apigenin on collagen-induced arthritis.

Apigenin (API) is a plant flavone that is known to exert a protective effect in rheumatoid arthritis (RA), which is a chronic autoimmune disease. However, the molecular mechanism for API's protective effect against RA is still unclear. Here, a collagen-induced arthritis (CIA) mouse model was used to assess the protective effect of API on RA. Histomorphological studies, immunohistochemistry, RT-PCR, and western blot were conducted to elucidate the roles of synovial hyperplasia, angiogenesis, and osteoclastogenesis in the protective effect of API on RA. Fibroblast-like synoviocytes (FLSs) were isolated to measure the effect of API on FLS proliferation and apoptosis. API exhibited a significant protective effect in CIA mice in a dose- and time-dependent manner. An increase in apoptosis and decrease in proliferation were observed after the API treatment in FLSs, suggesting that API might inhibit synovial hyperplasia. Moreover, CIA angiogenesis was repressed by API via down-regulation of VEGF and VEGFR. Furthermore, API regulated the osteoclastogenesis-associated RANKL/RANK/OPG system in CIA mice. Therefore, API inhibits CIA by repressing synovial hyperplasia, angiogenesis, and osteoclastogenesis. This suggested that API might be a putative low toxicity candidate drug for RA treatment.