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

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