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TGF-? mediates suppression of adipogenesis by estradiol through connective tissue growth factor induction.


ABSTRACT: In the bone marrow cavity, adipocyte numbers increase, whereas osteoblast progenitor numbers decrease with aging. Because adipocytes and osteoblasts share a common progenitor, it is possible that this shift is due to an increase in adipocyte-lineage cells at the expense of osteoblast-lineage commitment. Estrogens inhibit adipocyte differentiation, and in both men and women, circulating estrogens correlate with bone loss with aging. In bone cells, estrogens stimulate expression of TGF-? and suppress mesenchymal cell adipogenesis. Using a tripotential mesenchymal cell line, we have examined whether estradiol suppression of adipocyte differentiation is due to stimulation of TGF-? and the mechanism by which TGF-? suppresses adipogenesis. We observed that estradiol-mediated suppression of adipogenic gene expression required at least 48 h treatment. TGF-? expression increased within 24 h of estradiol treatment, and TGF-? inhibition reversed estradiol influences on adipogenesis and adipocyte gene expression. Connective tissue growth factor (CTGF) mediates TGF-? suppression of adipogenesis in mouse 3T3-L1 cells. CTGF expression was induced within 24 h of TGF-? treatment, whereas estradiol-mediated induction required 48 h treatment. Moreover, estradiol-mediated induction of CTGF was abrogated by TGF-? inhibition. These data support that estradiol effects on adipogenesis involves TGF-? induction, which then induces CTGF to suppress adipogenesis.

SUBMITTER: Kumar A 

PROVIDER: S-EPMC3249674 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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TGF-β mediates suppression of adipogenesis by estradiol through connective tissue growth factor induction.

Kumar Ashok A   Ruan Ming M   Clifton Kari K   Syed Farhan F   Khosla Sundeep S   Oursler Merry Jo MJ  

Endocrinology 20111108 1


In the bone marrow cavity, adipocyte numbers increase, whereas osteoblast progenitor numbers decrease with aging. Because adipocytes and osteoblasts share a common progenitor, it is possible that this shift is due to an increase in adipocyte-lineage cells at the expense of osteoblast-lineage commitment. Estrogens inhibit adipocyte differentiation, and in both men and women, circulating estrogens correlate with bone loss with aging. In bone cells, estrogens stimulate expression of TGF-β and suppr  ...[more]

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