Lady Davis Institute for Medical Research, McGill University, Montreal, QC H3T 1E2, Canada.
Biogerontology. 2009 Dec;10(6):747-55. doi: 10.1007/s10522-009-9221-7.
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.
与年龄相关的骨丢失与骨髓脂肪生成水平升高有关。雌激素（E2）已知可调节骨髓前体细胞向成骨细胞的分化，但它们在骨髓脂肪生成中的作用仍不清楚。E2 通过与其他核受体相互作用来调节皮下和内脏脂肪中的脂肪细胞分化。这种相互作用尚未在体内骨髓脂肪细胞中进行评估。在这项研究中，我们比较了两组动物，即年轻组和老年组，它们要么接受卵巢切除术（OVX），要么接受卵巢切除术加 E2（OVX+E2）替代治疗。我们发现，与年轻组相比，E2 的缺乏与 PPARc 水平升高和 Sirt1 水平降低更为显著相关，尤其是在老年组中。此外，老年小鼠对 E2 替代治疗的反应更好，表现在减少脂肪生成和 PPARc 表达，以及增加 Sirt1 表达水平。我们的研究结果代表了对 E2 在与年龄相关的骨丢失中的作用的新认识，这可能是通过调节骨髓内 Sirt1 表达来介导的。此外，这一证据表明，老年个体可能对 E2 治疗的反应更好，可逆转与年龄相关的骨丢失中所见的骨髓脂肪水平升高。
