10.
Age-related bone loss has been associated with high levels of marrow adipogenesis. Estrogens (E
2) are known to regulate the differentiation of marrow precursors into osteoblasts, however, their role in bone marrow adipogenesis
remain unknown. E
2 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 E
2 (OVX + E
2) replacement. We found that absence of E
2 was associated with higher levels of PPARγ and lower levels of Sirt1 most significantly in the old group. In addition, old
mice responded better to E
2 replacement in terms of reducing adipogenesis and PPARγ expression as well as increasing levels of Sirt1 expression. Our
findings represent a new understanding of the role of E
2 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 E
2 administration in terms of reverting the high levels of marrow fat seen in age-related bone loss.
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