Yamaguchi Noboru, Kukita Toshio, Li Yin-Ji, Kamio Noriaki, Fukumoto Satoshi, Nonaka Kazuaki, Ninomiya Yuzo, Hanazawa Shigemasa, Yamashita Yoshihisa
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.
FEBS Lett. 2008 Feb 6;582(3):451-6. doi: 10.1016/j.febslet.2007.12.037. Epub 2008 Jan 15.
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.
我们在此利用高效形成破骨细胞的RAW264细胞D克隆，研究脂联素是否能对肿瘤坏死因子-α（TNF-α）和核因子-κB受体激活因子配体（RANKL）诱导的破骨细胞生成产生抑制作用。球状脂联素（gAd）通过干扰肿瘤坏死因子受体相关因子6的产生和钙信号传导，强烈抑制TNF-α/RANKL诱导的破骨细胞分化；因此，活化T细胞核因子c1（NFATc1）的诱导受到强烈抑制。此外，我们观察到抑制AMP活化蛋白激酶可消除gAd对TNF-α/RANKL诱导的NFATc1表达的抑制作用。我们的数据表明，脂联素在与细胞因子激活相关的疾病中作为骨吸收的有效调节因子发挥作用。
