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Noggin Is Novel Inducer of Mesenchymal Stem Cell Adipogenesis IMPLICATIONS FOR BONE HEALTH AND OBESITY

  作者 Sawant, A; Chanda, D; Isayeva, T; Tsuladze, G; Garvey, WT; Ponnazhagan, S  
  选自 期刊  Journal of Biological Chemistry;  卷期  2012年287-15;  页码  12241-12249  
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[摘要]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/EBP delta, C/EBP alpha and peroxisome proliferator-activated receptor-gamma. 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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