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J Biol Chem. 2012 Apr 6;287(15):12241-9. doi: 10.1074/jbc.M111.293613. Epub 2012 Feb 20.

Noggin is novel inducer of mesenchymal stem cell adipogenesis: implications for bone health and obesity.

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  • 1Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

Abstract

Noggin is a glycosylated-secreted protein known so far for its inhibitory effects on bone morphogenetic protein (BMP) signaling by sequestering the BMP ligand. We report here for the first time a novel mechanism by which noggin directly induces adipogenesis of mesenchymal stem cells independently of major human adipogenic signals through C/EBPδ, C/EBPα and peroxisome proliferator-activated receptor-γ. Evaluation of a possible mechanism for noggin-induced adipogenesis of mesenchymal stem cells identified the role of Pax-1 in mediating such differentiation. The relevance of elevated noggin levels in obesity was confirmed in a preclinical, immunocompetent mouse model of spontaneous obesity and in human patients with higher body mass index. These data clearly provide a novel role for noggin in inducing adipogenesis and possibly obesity and further indicates the potential of noggin as a therapeutic target to control obesity.

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