Omentin-1 attenuates arterial calcification and bone loss in osteoprotegerin-deficient mice by inhibition of RANKL expression

Abstract

AimsOmentin-1 (also known as intelectin-1) is a recently identified visceral adipose tissue-derived cytokine that is inversely related to obesity. Our previous study showed that omentin-1 inhibits osteoblastic differentiation of calcifying vascular smooth muscle cells (CVSMCs) in vitro. This study was undertaken to investigate the effects of omentin-1 on arterial calcification and bone metabolism in vivo.Methods and resultsIn vitro, omentin-1 stimulated production of osteoprotegerin (OPG) and inhibited production of receptor activator for nuclear factor κB ligand (RANKL) in both CVSMCs and osteoblasts. In vivo, adenovirus-mediated over-expression of omentin-1 attenuated arterial calcification and bone loss in OPG -/- mice. All these in vitro and in vivo actions were abrogated by blockade of the PI3KAkt signalling pathway. Furthermore, omentin-1 reduced serum levels of RANKL, tartarate-resistant acid phosphatase-5b and osteocalcin, all of which are increased dramatically in OPG -/- mice.ConclusionThese data suggest that omentin-1 ameliorates arterial calcification and bone loss in vivo through the regulation of the RANK signalling pathway. © 2011 The Author.