Osteocyte-intrinsic mTORC1 signaling restrains trabecular bone accrual in mice
Osteocyte-intrinsic mTORC1 signaling restrains trabecular bone accrual in mice
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骨细胞固有的 mTORC1 信号传导抑制小鼠小梁骨的生长
DOI：
10.1002/jcb.27470
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发表时间：
2018-11-01
影响因子：
4
通讯作者：
Chen, Jianquan
中科院分区：
文献类型：
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作者：
Liu, Qingbai;Liu, Cunchang;Chen, Jianquan
雷帕霉素（mTOR）复合物1（mTORC 1）信号转导机制通过调节成骨细胞分化的多个步骤及其活性在骨稳态中发挥重要的生理作用。然而，其在骨细胞中的潜在作用尚未被探索。在这项研究中，我们删除了猛禽，一个特定的和必要的组成部分mTORC 1，在骨细胞中使用Dmp 1-Cre。骨细胞中Raptor的缺失不影响骨的发育和生长，但对骨量产生了特定的影响。骨细胞特异性Raptor基因缺失对皮质骨间室无明显影响，但导致骨小梁质量增加。从机制上讲，Raptor缺失导致骨吸收减少而不改变骨形成活性。因此，我们的研究揭示了骨细胞内在mTORC 1信号传导在限制骨小梁骨量中的意想不到的作用，表明骨细胞特异性抑制mTORC 1可用作治疗骨质疏松症的新方法。
Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) signaling plays important physiological roles in bone homeostasis by regulating multiple steps of osteoblast differentiation as well as its activity. However, its potential role in osteocytes has not been explored. In this study, we deleted Raptor, a specific and essential component of mTORC1, in osteocytes using Dmp1-Cre. Deletion of Raptor in osteocytes did not affect bone development and growth, but caused compartment-specific effects on bone mass. Osteocyte-specific deletion of Raptor had no obvious effect on cortical bone compartments, but led to increased trabecular bone mass. Mechanistically, Raptor deletion resulted in decreased bone resorption without altering bone formation activity. Thus, our study revealed an unexpected role of osteocyte-intrinsic mTORC1 signaling in limiting trabecular bone mass, suggesting that osteocyte-specific inhibition of mTORC1 may be used as a novel approach to treatment of osteoporosis.