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机械门控TRPV4在材料诱导骨形成中的作用机制研究进展
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Abstract:
具有特定理化性质的骨诱导生物材料无需外源细胞或生长因子可在远离宿主骨部位诱导成骨，在大段骨缺损修复中极具应用前景。然而，材料诱导成骨机制尚未阐明，限制了材料的优化。随着学科之间的交叉融合，近年来机械转导被广泛关注。机械转导是细胞感知材料表面微结构等介导的机械应力刺激并将其转化为生物化学信号的过程，而细胞微环境中机械应力信号的感知主要通过机械敏感离子通道介导。瞬时受体电位香草素受体4型通道蛋白(Transient Receptor Potential Vanilloid 4, TRPV4)作为机械敏感通道是细胞感知微环境力学信号的核心分子，在骨诱导过程中扮演重要角色。本文系统综述了TRPV4的结构、功能及其在生理性骨改建和材料诱导成骨中的作用，并探讨了靶向TRPV4通道优化骨诱导生物材料的设计策略，以期为新一代骨诱导材料的优化设计提供理论参考。
Bone-inducing biomaterials with specific physicochemical properties can induce osteogenesis at sites far from the host bone without exogenous cells or growth factors, showing great application prospects in the repair of large bone defects. However, the mechanism of osteogenesis induced by materials remains unclear, which limits the optimization of materials. With the cross-integration of disciplines, mechanical transduction has attracted extensive attention in recent years. Mechanical transduction is the process by which cells sense mechanical stress stimuli mediated by material surface microstructures and convert them into biochemical signals, and the perception of mechanical stress signals in the cellular microenvironment is mainly mediated by mechanosensitive ion channels. Transient Receptor Potential Vanilloid 4 (TRPV4) channel protein, as a mechanosensitive channel, is a core molecule for cells to sense mechanical signals in the microenvironment and plays an important role in the process of bone induction. This article systematically reviews the structure, function of TRPV4 and its role in physiological bone remodeling and material-induced osteogenesis, and discusses the design strategies for optimizing bone-inducing biomaterials by targeting TRPV4 channels, with the aim of providing theoretical references for the optimized design of the next generation of bone-inducing materials.
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