Hormone‐sensitive lipase‐knockout mice maintain high bone density during aging-猫眼课题宝

DOI：

10.1096/fj.11-181016

发表时间：

2011-08

期刊：

The FASEB Journal

影响因子：

通讯作者：

中科院分区：

其他

文献类型：

作者：

W. Shen;Li-fen Liu;Shailja Patel;F. Kraemer

我们验证了一种假设，即激素敏感脂肪酶(HSL)的作用会影响骨髓的微环境，通过基因缺失去除HSL功能会在衰老小鼠中保持高骨量。我们比较了窝龄对照野生型(WT)和HSL-/-小鼠在衰老过程中血清生化值的变化，用微型计算机断层扫描的骨小梁密度，骨组织形态计量学，以及原代骨髓细胞和成骨细胞的特征。在衰老过程中，HSL和参与脂质代谢的基因在骨髓中有受调控的表达。HSL-/-小鼠血清胰岛素和骨钙素水平升高，瘦素水平下降。与14个月时WT小鼠骨髓中脂肪细胞的显著浸润(按面积计为65%)相比，HSL-/-小鼠骨髓中的脂肪细胞较少(16%，P&lt；0.05)且体积较小。在峰值骨密度相近的情况下，HSL-/-小鼠的骨密度(骨体积/总体积)随年龄增长保持较高(骨体积/总体积的6.1%)，高于WT小鼠(2.6%，P&lt；0.05)。来自HSL-/-小鼠的原代成骨细胞生长速度加快，成骨能力增强，表现为Runx2(3.5倍，P&lt；0.05)和骨钙素(4倍，P&lt；0.05)的表达增加。HSL的缺失引导骨髓中的细胞向成骨细胞分化，并有利于随着年龄的增长保持骨密度。-沈，W.J.，Liu，L.F.，Patel，S.，Kraemer，F.B.激素敏感型脂肪酶基因敲除小鼠在衰老过程中保持高骨密度。FASE B J.25,2722-2730(2011)。Www.fasebj.org

We tested the hypothesis that the actions of hormone‐sensitive lipase (HSL) affect the microenvironment of the bone marrow and that removal of HSL function by gene deletion maintains high bone mass in aging mice. We compared littermate control wild‐type (WT) and HSL‐/‐ mice during aging for changes in serum biochemical values, trabecular bone density using micro‐computed tomography, bone histomorphometry, and characteristics of primary bone marrow cells and preosteoblasts. There is a regulated expression of HSL and genes involved in lipid metabolism in the bone marrow during aging. HSL‐/‐ mice have increased serum levels of insulin and osteocalcin with decreased leptin levels. Compared with the marked adipocyte infiltration in WT bone marrow (65% by area) at 14 mo, HSL‐/‐ mice have fewer (16%, P<0.05) and smaller adipocytes in bone marrow. While peak bone density is similar, HSL‐/‐ mice maintain a higher bone density (bone volume/total volume 6.1%) with age than WT mice (2.6%, P<0.05). Primary osteoblasts from HSL‐/‐ mice show increased growth rates and higher osteogenic potential, manifested by increased expression of Runx2 (3.5‐fold, P<0.05) and osteocalcin (4‐fold, P<0.05). The absence of HSL directs cells within the bone marrow toward osteoblast differentiation and favors the maintenance of bone density with aging.—Shen, W.‐J., Liu, L.‐F., Patel, S., Kraemer, F. B. Hormone‐sensitive lipase‐knockout mice maintain high bone density during aging. FASEB J. 25, 2722‐2730 (2011). www.fasebj.org

Hormone‐sensitive lipase‐knockout mice maintain high bone density during aging

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