Thesis or Dissertation Sclerostin enhances adipocyte differentiation in 3T3-L1 cells

浮田, 万由美

Sclerostin, a secreted protein encoded by the Sost gene, is produced byosteocytes and is inhibited by osteoblast differentiation and bone formation. Recently, afunctional association between bone and fat tissue has been suggested, and acorrelation between circulating sclerostin levels and lipid metabolism has been reportedin humans. However, the effects of sclerostin on adipogenesis remain unexplored. Inthe present study, we examined the role of sclerostin in regulating adipocytedifferentiation using 3T3-L1 preadipocytes. In these cells, sclerostin enhancedadipocyte-specific gene expression and the accumulation of lipid deposits. Sclerostinalso upregulated CCAAT/enhancer binding protein β expression but not cellproliferation and caspase-3/7 activities. Sclerostin also attenuated canonicalWnt3a-inhibited adipocyte differentiation. Recently, the transcriptional modulator TAZhas been involved in the canonical Wnt signaling pathway. Sclerostin reducedTAZ-responsive transcriptional activity and TAZ-responsive gene expression.Transfection of 3T3-L1 cells with TAZ siRNA increased the lipid deposits andadipogenic gene expression. These results show that sclerostin upregulates adipocytedifferentiation in 3T3-L1 cells, suggesting a possible role for the osteocyte-derivedsclerostin as a regulator of fat metabolism and as a reciprocal regulator of bone andadipose tissues metabolism.
Hokkaido University(北海道大学). 博士(歯学)

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