title: Sclerostin Enhances Adipocyte Differentiation in 3T3-L1 Cells.
abstract: Sclerostin, a secreted protein encoded by the Sost gene, is produced by osteocytes and is inhibited by osteoblast differentiation and bone formation. Recently, a functional association between bone and fat tissue has been suggested, and a correlation between circulating sclerostin levels and lipid metabolism has been reported in humans. However, the effects of sclerostin on adipogenesis remain unexplored. In the present study, we examined the role of sclerostin in regulating adipocyte differentiation using 3T3-L1 preadipocytes. In these cells, sclerostin enhanced adipocyte-specific gene expression and the accumulation of lipid deposits. Sclerostin also upregulated CCAAT/enhancer binding protein β expression but not cell proliferation and caspase-3/7 activities. Sclerostin also attenuated canonical Wnt3a-inhibited adipocyte differentiation. Recently, the transcriptional modulator TAZ has been involved in the canonical Wnt signaling pathway. Sclerostin reduced TAZ-responsive transcriptional activity and TAZ-responsive gene expression. Transfection of 3T3-L1 cells with TAZ siRNA increased the lipid deposits and adipogenic gene expression. These results show that sclerostin upregulates adipocyte differentiation in 3T3-L1 cells, suggesting a possible role for the osteocyte-derived sclerostin as a regulator of fat metabolism and as a reciprocal regulator of bone and adipose tissues metabolism.
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586, Japan.|Department of Crown and Bridge Prosthodontics, Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ukita
authors.affiliation: Department of Crown and Bridge Prosthodontics, Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586, Japan.
authors.forename: Taihiko
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Department of Crown and Bridge Prosthodontics, Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Ohata
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Tamura
mesh_terms: D041721:3T3-L1 Cells; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D050156:Adipogenesis; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D050356:Lipid Metabolism; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D047495:PPAR gamma; C486030:Sost protein, mouse; D015534:Trans-Activators; C517794:Wwtr1 protein, mouse; D053148:Caspase 3
keywords: ADIPOCYTE; OSTEOCYTE; SCLEROSTIN; SOST