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

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 PPAR gamma 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 PPAR gamma 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.