Li Yijie, Yang Yanyan, Wang Xiaohuan, Li Long, Zhou Mouwang
Department of Rehabilitation Medicine, Peking University Third Hospital, 49 North Garden Road, Beijing, 100191, China.
State Key Laboratory of Nonlinear Mechanics and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, 100190, China.
Commun Biol. 2025 Mar 29;8(1):515. doi: 10.1038/s42003-025-07946-8.
For precise bone formation, osteoblasts need to accurately migrate to specific sites guided by various biochemical and mechanical cues. During this migration, fluctuations in extracellular osmolarity may arise from shifts in the surrounding fluid environment. However, as a main regulator of cell morphology and function, whether the extracellular osmolarity change may affect osteoblast migration remains unclear. Here, we provide evidence showing that changes in extracellular osmolarity significantly impact osteoblast migration, with a hypotonic environment enhancing it while a hypertonic environment inhibiting it. Further, our findings reveal that a hypotonic treatment increases intracellular pressure, activating the Transient Receptor Potential Vanilloid 4 (TRPV4) channel. This activation of TRPV4 modulates stress fibers, focal adhesions (FAs), and cell polarity through the Rho/ROCK signaling pathway, ultimately impacting osteoblast migration. Our findings provide valuable insights into the significant influence of extracellular osmolarity on osteoblast migration, which has potential implications for enhancing our understanding of bone remodeling.
为了实现精确的骨形成，成骨细胞需要在各种生化和机械信号的引导下准确迁移到特定部位。在这个迁移过程中，细胞外渗透压的波动可能源于周围流体环境的变化。然而，作为细胞形态和功能的主要调节因子，细胞外渗透压的变化是否会影响成骨细胞迁移仍不清楚。在这里，我们提供的证据表明，细胞外渗透压的变化显著影响成骨细胞迁移，低渗环境促进其迁移，而高渗环境则抑制其迁移。此外，我们的研究结果表明，低渗处理会增加细胞内压力，激活瞬时受体电位香草酸受体4（TRPV4）通道。TRPV4的这种激活通过Rho/ROCK信号通路调节应力纤维、粘着斑（FAs）和细胞极性，最终影响成骨细胞迁移。我们的研究结果为细胞外渗透压对成骨细胞迁移的重大影响提供了有价值的见解，这对于增进我们对骨重塑的理解具有潜在意义。
