Adiponectin inhibits induction of TNF-α/RANKL-stimulated NFATc1 via the AMPK signaling

Edited by Laszlo Nagy

Received 31 August 2007; received in revised form 19 December 2007; accepted 22 December 2007. published online 15 January 2008.

Abstract

We investigated here whether adiponectin can exhibit an inhibitory effect on tumor necrosis factor-alpha (TNF-α)- and receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis by using RAW264 cell D clone with a high efficiency to form osteoclasts. Globular adiponectin (gAd) strongly inhibited TNF-α/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-α/RANKL-induced NFATc1 expression. Our data suggest that adiponectin acts as a potent regulator of bone resorption observed in diseases associated with cytokine activation.

Abbreviations: 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

Keywords: Adiponectin, AMP-activated protein kinase, Calcium signaling, Osteoclastogenesis, Receptor activator of nuclear factor-κB ligand, Nuclear factor of activated T cells c1

a 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

b Oral Cellular and Molecular Biology, Kyushu University Faculty of Dental Science, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan

c Department of Preventive Dentistry, Kyushu University Faculty of Dental Science, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan

d Section of Oral Neuroscience, Kyushu University Faculty of Dental Science, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan

e Department of Applied Biological Sciences, College of Bioresource Science, Nihon University, Kameino, Fujisawa-City, Kanagawa 292-8510, Japan

Corresponding author. Fax: +81 92 642 6468.

PII: S0014-5793(08)00014-8

doi:10.1016/j.febslet.2007.12.037

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