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雷帕霉素靶蛋白在骨质疏松症中的治疗作用

Mammalian target of rapamycin as a therapeutic target in osteoporosis.

机构信息

Guangzhou University of Chinese Medicine, Guangzhou, China.

Department of Spinal Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

出版信息

J Cell Physiol. 2018 May;233(5):3929-3944. doi: 10.1002/jcp.26161. Epub 2017 Sep 28.

Abstract

The mechanistic target of rapamycin (mTOR) plays a key role in sensing and integrating large amounts of environmental cues to regulate organismal growth, homeostasis, and many major cellular processes. Recently, mounting evidences highlight its roles in regulating bone homeostasis, which sheds light on the pathogenesis of osteoporosis. The activation/inhibition of mTOR signaling is reported to positively/negatively regulate bone marrow mesenchymal stem cells (BMSCs)/osteoblasts-mediated bone formation, adipogenic differentiation, osteocytes homeostasis, and osteoclasts-mediated bone resorption, which result in the changes of bone homeostasis, thereby resulting in or protect against osteoporosis. Given the likely importance of mTOR signaling in the pathogenesis of osteoporosis, here we discuss the detailed mechanisms in mTOR machinery and its association with osteoporosis therapy.

摘要

雷帕霉素靶蛋白(mTOR)在感知和整合大量环境线索以调节机体生长、内稳态和许多主要细胞过程方面发挥着关键作用。最近,越来越多的证据强调了其在调节骨内稳态中的作用,这为骨质疏松症的发病机制提供了线索。mTOR 信号的激活/抑制被报道可正向/负向调节骨髓间充质干细胞(BMSCs)/成骨细胞介导的骨形成、成脂分化、骨细胞稳态和破骨细胞介导的骨吸收,导致骨内稳态的变化,从而导致或预防骨质疏松症。鉴于 mTOR 信号在骨质疏松症发病机制中的重要性,我们在这里讨论了 mTOR 机制及其与骨质疏松症治疗的关联的详细机制。

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