Mechanical stimulation prevents osteocyte apoptosis: requirement of integrins, Src kinases, and ERKs
Mechanical stimulation prevents osteocyte apoptosis: requirement of integrins, Src kinases, and ERKs
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DOI：
10.1152/ajpcell.00278.2004
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发表时间：
2005-09-01
影响因子：
5.5
通讯作者：
Bellido, T
中科院分区：
文献类型：
--
作者：
Plotkin, LI;Mathov, I;Bellido, T
骨细胞，埋藏在骨基质中的前成骨细胞，形成一个广泛的细胞通讯网络，被认为可以检测微损伤和机械应变，并传递导致修复和代偿性骨增加或减少的信号。骨活性激素和药物通过调节骨细胞凋亡来控制这个网络的完整性，这可能是骨强度的决定因素。在这里，我们证明了拉伸的机械刺激激活ERKs，这反过来又负责骨细胞凋亡的衰减。骨细胞拉伸的作用通过整合素、细胞骨架和催化分子（如Src激酶）传递。拉伸诱导的抗凋亡也需要ERKs的核易位和新的基因转录。将机械刺激、整合素/细胞骨架/Src/ERK信号通路的激活和骨细胞存活联系起来的证据，为机械力（或缺乏机械力）对骨骼健康和疾病的深远作用提供了机制基础。
Osteocytes, former osteoblasts entombed in the bone matrix, form an extensive cell communication network that is thought to detect microdamage and mechanical strains and to transmit signals leading to repair and compensatory bone augmentation or reduction. Bone active hormones and drugs control the integrity of this network by regulating osteocyte apoptosis, which might be a determinant of bone strength. Herein we demonstrate that mechanical stimulation by stretching activates the ERKs, which in turn are responsible for the attenuation of osteocyte apoptosis. The effect of osteocyte stretching is transmitted by integrins and cytoskeletal and catalytic molecules, such as Src kinases. Stretch-induced antiapoptosis also requires nuclear translocation of ERKs and new gene transcription. The evidence linking mechanical stimulation, activation of an integrin/cytoskeleton/Src/ERK signaling pathway, and osteocyte survival provides a mechanistic basis for the profound role of mechanical forces, or lack thereof, on skeletal health and disease.