Xie Jing, Zhou Chenchen, Zhang Demao, Cai Linyi, Du Wei, Li Xiaobing, Zhou Xuedong
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610064, China.
ACS Appl Bio Mater. 2018 Sep 17;1(3):792-801. doi: 10.1021/acsabm.8b00246. Epub 2018 Aug 24.
Bone shows the potential to adapt its architecture to environmental rigidity via the bone remodeling process, which is governed by osteocytes. Once the remodeling process is disrupted, the mechanics of the bone architecture is impaired, and bone disease proceeds. During the process of pathogenesis, how the osteocytes start the process of sensing and transducing a weakened extracellular mechanical signal into a biochemical signal remains elusive. In the current study, using polydimethylsiloxane (PDMS) substrates with varied mechanical stiffnesses, we first showed that the osteocytes can sense the mechanical change and respond by showing different cell spreading areas and cytoskeleton distributions. Osteocytes sense ECM mechanics via integrin αvβ3, which interacts with focal adhesion kinase (FAK) to promote the transduction of extracellular mechanical stimuli into intracellular biochemical signals. FAK triggers cytoplasmic β-catenin signaling and the resultant nuclear translocation. This signaling results in changes in the gap junction and mineralization activity of the osteocytes. This study establishes the correlation between microenvironmental mechanics and osteocyte function by characterizing the interaction between integrin αvβ3/FAK signaling and β-catenin signaling, thus providing a deep understanding of mechanosensing and mechanotransduction in osteocytes and bone pathogenesis.
骨骼具有通过骨重塑过程使其结构适应环境硬度的潜力，该过程由骨细胞控制。一旦重塑过程被破坏，骨骼结构的力学性能就会受损，进而引发骨疾病。在发病过程中，骨细胞如何启动将减弱的细胞外机械信号感知并转化为生化信号的过程仍不清楚。在当前的研究中，我们使用具有不同机械刚度的聚二甲基硅氧烷（PDMS）底物，首先表明骨细胞能够感知机械变化，并通过显示不同的细胞铺展面积和细胞骨架分布做出反应。骨细胞通过整合素αvβ3感知细胞外基质力学，整合素αvβ3与粘着斑激酶（FAK）相互作用，促进细胞外机械刺激向细胞内生化信号的转导。FAK触发细胞质β-连环蛋白信号传导及随后的核转位。该信号传导导致骨细胞的缝隙连接和矿化活性发生变化。本研究通过表征整合素αvβ3/FAK信号传导与β-连环蛋白信号传导之间的相互作用，建立了微环境力学与骨细胞功能之间的相关性，从而为深入了解骨细胞中的机械传感和机械转导以及骨发病机制提供了依据。
