title: Noggin is novel inducer of mesenchymal stem cell adipogenesis: implications for bone health and obesity.
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.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Anandi
authors.initials: A
authors.lastname: Sawant
authors.forename: Diptiman
authors.initials: D
authors.lastname: Chanda
authors.forename: Tatyana
authors.initials: T
authors.lastname: Isayeva
authors.forename: George
authors.initials: G
authors.lastname: Tsuladze
authors.forename: W T
authors.initials: WT
authors.lastname: Garvey
authors.forename: Selvarangan
authors.initials: S
authors.lastname: Ponnazhagan
mesh_terms: D050156:Adipogenesis; D050154:Adiposity; D000328:Adult; D000818:Animals; D015519:Bone Density; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000235:genetics / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D051761:Paired Box Transcription Factors / Q000378:metabolism; D055815:Young Adult; D000099176:Noggin Protein
chemical_list: D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins; D047495:PPAR gamma; D051761:Paired Box Transcription Factors; D000099176:Noggin Protein; C530718:CEBPA protein, mouse; C497253:Cebpd protein, mouse; C070835:PAX1 transcription factor