Loss of Rictor with aging in osteoblasts promotes age-related bone loss
Loss of Rictor with aging in osteoblasts promotes age-related bone loss
复制标题
随着成骨细胞衰老，Rictor 的丢失会促进与年龄相关的骨质流失
DOI：
10.1038/cddis.2016.249
复制
发表时间：
2016-10-01
影响因子：
9
通讯作者：
Bai, Xiaochun
中科院分区：
文献类型：
--
作者：
Lai, Pinling;Song, Qiancheng;Bai, Xiaochun
成骨细胞功能障碍是年龄相关性骨质流失的主要原因，但成骨细胞功能随年龄变化的潜在机制尚不清楚。本研究表明，老龄小鼠成骨细胞在体内和体外均表现出明显的骨形成表面粘附受损和矿化降低。Rictor是控制细胞骨架组织和细胞存活的雷帕霉素复合物2 （mTORC2）机制靶点的一个特定成分，在成骨细胞中随着年龄的增长而下调。在机制上，我们发现随着年龄的增长活性氧水平的增加刺激miR-218的表达，miR-218直接靶向Rictor，降低成骨细胞骨表面粘附和存活，导致老年小鼠功能成骨细胞数量减少，加速骨质流失。我们的研究结果揭示了一种新的功能途径，对年龄相关性骨质流失很重要，并支持miR-218和Rictor作为年龄相关性骨质疏松症治疗干预的潜在靶点。
Osteoblast dysfunction is a major cause of age-related bone loss, but the mechanisms underlying changes in osteoblast function with aging are poorly understood. This study demonstrates that osteoblasts in aged mice exhibit markedly impaired adhesion to the bone formation surface and reduced mineralization in vivo and in vitro. Rictor, a specific component of the mechanistic target of rapamycin complex 2 (mTORC2) that controls cytoskeletal organization and cell survival, is downregulated with aging in osteoblasts. Mechanistically, we found that an increased level of reactive oxygen species with aging stimulates the expression of miR-218, which directly targets Rictor and reduces osteoblast bone surface adhesion and survival, resulting in a decreased number of functional osteoblasts and accelerated bone loss in aged mice. Our findings reveal a novel functional pathway important for age-related bone loss and support for miR-218 and Rictor as potential targets for therapeutic intervention for age-related osteoporosis treatment.