Extracellular osmolarity regulates osteoblast migration through the TRPV4-Rho/ROCK signaling

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.