AG490 inhibits NFATc1 expression and STAT3 activation during RANKL induced osteoclastogenesis精选.pdf

Biochemical and Biophysical Research Communications 435 (2013) 533–539 Contents lists available at SciVerse ScienceDirect Biochemical and Biophysical Research Communications journal homepage: www.else /locate/ybbrc AG490 inhibits NFATc1 expression and STAT3 activation during RANKL induced osteoclastogenesis Chang-hong Li, Jin-xia Zhao, Lin Sun, Zhong-qiang Yao, Xiao-li Deng, Rui Liu, Xiang-yuan Liu ⇑ Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing 100191, PR China a r t i c l e i n f o a b s t r a c t Article history: Commonly, JAK/STAT relays cytokine signals for cell activation and proliferation, and recent studies have Received 16 April 2013 shown that the elevated expression of JAK/STAT is associated with the immune rejection of allografts and Available online 7 May 2013 the inflammatory processes of autoimmune disease. However, the role which JAK2/STAT3 signaling plays in the receptor activator of nuclear factor-jB ligand (RANKL)-mediated osteoclastogenesis is unknown. In Keywords: this study, we investigated the effects of AG490, specific JAK2 inhibitor, on osteoclast differentiation Osteoclastogenesis in vitro. AG490 significantly inhibited osteoclastogenesis in murine osteoclast precursor cell line AG490 RAW264.7 induced by RANKL. AG490 suppressed cell proliferation and delayed the G1 to S cell cycle RANKL NFATc1 transition. Furthermore, AG490 also suppressed the expressio