Mice Lacking β-Adrenergic Receptors Have Increased Bone Mass but Are Not Protected from Deleterious Skeletal Effects of Ovariectomy
Mice Lacking β-Adrenergic Receptors Have Increased Bone Mass but Are Not Protected from Deleterious Skeletal Effects of Ovariectomy
复制标题
缺乏β-肾上腺素能受体的小鼠骨量增加，但无法免受卵巢切除术对骨骼的有害影响
DOI：
10.1210/en.2008-0843
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发表时间：
2009-01-01
期刊：
影响因子：
4.8
通讯作者：
Ferrari, S. L.
中科院分区：
文献类型：
--
作者：
Bouxsein, M. L.;Devlin, M. J.;Ferrari, S. L.
β2-肾上腺素能受体的激活抑制成骨细胞骨形成并增强破骨细胞骨吸收。 β受体阻滞剂是否能抑制卵巢切除术引起的骨质流失并降低骨折风险仍存在争议。为了进一步探讨β-肾上腺素能信号在骨骼获得和雌激素缺乏反应中的作用，我们评估了缺乏三种已知β-肾上腺素能受体（β-less）的小鼠。雄性β-less小鼠的体重、脂肪百分比和骨矿物质密度显着高于野生型（WT）小鼠，并且随着年龄的增长更是如此。与它们更大的脂肪量一致，β-less 小鼠的血清瘦素显着高于 WT 小鼠。成年 β-less 小鼠的股骨中段横截面积和皮质厚度显着高于 WT 小鼠，股骨生物力学特性也是如此（+28% 至 +49%，P < 0.01）。年轻男性β-less具有比WT更高的椎骨（1.3倍）和股骨远端（3.5倍）骨小梁体积（两者P < 0.001）和更低的破骨细胞表面。随着年龄的增长，这些差异逐渐缩小，组织学证据显示，与 WT 小鼠相比，β-less 小鼠股骨远端的破骨细胞表面增加，骨形成率降低。与 8-16 周龄的 WT 小鼠相比，β-less 小鼠的血清抗酒石酸碱性磷酸酶 5B 升高（P < 0.01）。在β-less和WT小鼠中，卵巢切除术抑制骨量增加并减少小梁骨体积/总体积。总而言之，这些数据表明，β-肾上腺素能信号传导的缺失会导致男性肥胖和皮质骨量增加，但并不能阻止雌激素缺乏对骨小梁微结构的有害影响。我们的研究结果还表明，体重和/或瘦素对骨转换和皮质骨结构有直接的积极影响，与肾上腺素能信号传导无关。 （内分泌学 150：144-152，2009）
Activation of beta 2-adrenergic receptors inhibits osteoblastic bone formation and enhances osteoclastic bone resorption. Whether beta-blockers inhibit ovariectomy-induced bone loss and decrease fracture risk remains controversial. To further explore the role of beta-adrenergic signaling in skeletal acquisition and response to estrogen deficiency, we evaluated mice lacking the three known beta-adrenergic receptors (beta-less). Body weight, percent fat, and bone mineral density were significantly higher in male beta-less than wild-type (WT) mice, more so with increasing age. Consistent with their greater fat mass, serum leptin was significantly higher in beta-less than WT mice. Mid-femoral cross-sectional area and cortical thickness were significantly higher in adult beta-less than WT mice, as were femoral biomechanical properties (+28 to +49%, P < 0.01). Young male beta-less had higher vertebral (1.3-fold) and distal femoral (3.5-fold) trabecular bone volume than WT (P < 0.001 for both) and lower osteoclast surface. With aging, these differences lessened, with histological evidence of increased osteoclast surface and decreased bone formation rate at the distal femur in beta-less vs. WT mice. Serum tartrate-resistance alkaline phosphatase-5B was elevated in beta-less compared with WT mice from 8-16 wk of age (P < 0.01). Ovariectomy inhibited bone mass gain and decreased trabecular bone volume/total volume similarly in beta-less and WT mice. Altogether, these data indicate that absence of beta-adrenergic signaling results in obesity and increased cortical bone mass in males but does not prevent deleterious effects of estrogen deficiency on trabecular bone microarchitecture. Our findings also suggest direct positive effects of weight and/or leptin on bone turnover and cortical bone structure, independent of adrenergic signaling. (Endocrinology 150: 144-152, 2009)