Adiponectin inhibits induction of TNF-alpha/RANKL-stimulated NFATc1 via the AMPK signaling |
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Authors: | Yamaguchi Noboru Kukita Toshio Li Yin-Ji Kamio Noriaki Fukumoto Satoshi Nonaka Kazuaki Ninomiya Yuzo Hanazawa Shigemasa Yamashita Yoshihisa |
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Affiliation: | Section of Pediatric Dentistry, Division of Oral Health, Growth and Development, Kyushu University Faculty of Dental Science, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. nyama@dent.kyushu-u.ac.jp |
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Abstract: | We investigated here whether adiponectin can exhibit an inhibitory effect on tumor necrosis factor-alpha (TNF-alpha)- and receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclastogenesis by using RAW264 cell D clone with a high efficiency to form osteoclasts. Globular adiponectin (gAd) strongly inhibited TNF-alpha/RANKL-induced differentiation of osteoclasts by interfering with TNF receptor-associated factor 6 production and calcium signaling; consequently, the induction of nuclear factor of activated T cells c1 (NFATc1) was strongly inhibited. Moreover, we observed that inhibition of AMP-activated protein kinase abrogated gAd inhibition for TNF-alpha/RANKL-induced NFATc1 expression. Our data suggest that adiponectin acts as a potent regulator of bone resorption observed in diseases associated with cytokine activation. |
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Keywords: | AMPK, AMP-activated protein kinase gAd, globular adiponectin MAPK, mitogen-activated protein kinase NFATc1, nuclear factor of activated T cells c1 NF-κB, nuclear factor-κB TNF-α, tumor necrosis factor-alpha TRAF6, TNF receptor-associated factor 6 RANKL, receptor activator of NF-κB ligand |
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