Adiponectin inhibits induction of TNF-alpha/RANKL-stimulated NFATc1 via the AMPK signaling.
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.
Yamaguchi
Noboru
N
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
Kukita
Toshio
T
Li
Yin-Ji
YJ
Kamio
Noriaki
N
Fukumoto
Satoshi
S
Nonaka
Kazuaki
K
Ninomiya
Yuzo
Y
Hanazawa
Shigemasa
S
Yamashita
Yoshihisa
Y
D055372:AMP-Activated Protein Kinases; D052242:Adiponectin / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D001847:Bone Diseases / Q000201:enzymology; D001862:Bone Resorption / Q000201:enzymology; D015536:Down-Regulation / Q000187:drug effects; D004338:Drug Combinations; D004789:Enzyme Activation; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism / Q000502:physiology*; D050778:NFATC Transcription Factors / Q000378:metabolism*; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*; D053245:RANK Ligand / Q000494:pharmacology*; D054419:Receptors, Adiponectin / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D052242:Adiponectin; C499919:Adipoq protein, mouse; D004338:Drug Combinations; D009097:Multienzyme Complexes; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D053245:RANK Ligand; D054419:Receptors, Adiponectin; D014409:Tumor Necrosis Factor-alpha; C475419:adiponectin receptor 1, mouse; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases