Effect of estrogens on bone marrow adipogenesis and Sirt1 in aging C57BL/6J mice

Lady Davis Institute for Medical Research, McGill University, Montreal, QC H3T 1E2, Canada.
Biogerontology (Impact Factor: 3.29). 04/2009; 10(6):747-55. DOI: 10.1007/s10522-009-9221-7
Source: PubMed


Age-related bone loss has been associated with high levels of marrow adipogenesis. Estrogens (E2) are known to regulate the differentiation of marrow precursors into osteoblasts, however, their role in bone marrow adipogenesis remain unknown. E2 regulate adipocyte differentiation in subcutaneous and visceral fat through interaction with other nuclear receptors. This interaction has not been assessed in bone marrow adipocytes in vivo. In this study, we compared two groups of animals, young and old, after either oophorectomy (OVX) or oophorectomy plus E2 (OVX + E2) replacement. We found that absence of E2 was associated with higher levels of PPARc and lower levels of Sirt1 most significantly in the old group. In addition, old mice responded better to E2 replacement in terms of reducing adipogenesis and PPARc expression as well as increasing levels of Sirt1 expression. Our findings represent a new understanding of the role of E2 in age-related bone loss, which could be mediated through the regulation of Sirt1 expression within the bone marrow. In addition, this evidence suggests that old individuals may show a better response to E2 administration in terms of reverting the high levels of marrow fat seen in age-related bone loss.

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    • "In culture experiments , serum from postmenopausal women induced greater adipogenic differentiation of stromal precursors, however hormone replacement did not reverse the adipogenic differentiation observed in vitro [60]. In addition, OVX mice have been illustrated to have an increased adipogenic marrow, accompanied by a reduction in Sirt1 protein expression and an increase in PPAR-γ protein, which were reversed by estrodial administration [59]. The above investigations illustrate an overall disruption to steady-state functioning of the bone marrow microenvironment both independent and dependent on estrogen in ageing and menopause. "
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