流体剪切应力对骨细胞分子活动的影响

Flow shear stress induced molecular events of bone cells

机械应力在骨的生长、重建过程中起着十分重要的作用。应力刺激作用于骨组织后对应力感受细胞(骨细胞、成骨细胞)产生牵张应力及流体剪切应力(FSS)刺激,进而影响细胞内相关基因的表达,在此过程中流体剪切应力占主导作用。目前FSS引起骨细胞分子活动的具体机制还不明确,细胞膜上的应力敏感离子通道、整合素-细胞骨架复合体以及缝隙连接/CX43半通道结构可能在力学信号转导过程中起重要作用,它们可能通过促分裂原活化蛋白激酶(Mitogen- activated protein kinase,MAPK)通路、蛋白激酶A/蛋白激酶C(PKA/PKC)通路、核因子κB(NFκB)通路、RhoA/Rho-激酶(RohA-dependent kinase,ROCK)通路以及Ca^(2+)通路起作用,最终影响细胞生长因子、转录因子以及成骨相关基质蛋白的表达。FSS影响骨细胞分子活动的应力传导以及信号转导的确切机制仍需要进一步阐明。

Mechanical stress plays an important role in bone growth and bone remodeling. It causes stretch stress and fluid flow shear stress, which can be sensed by mecheno-sensory cells, e.g. osteocyte and osteoblast, and induces changes of gene expression in those cells. The fluid flow shear stress is thought to be the main stimulin in this process. However, up to now, it is still not clear for what signals are triggered in mecheno-sensory cells end how the flow shear stress exactly affects the expression of specific proteins. Evidences have shown that the stress-sensitive cation channels, the integrin-cytoskeleton complexes and the gap junction/CX43 hemi-chennels may be key players in transducing mechanical signals, presumably via mitogen-activated protein kinase pathway, PKA/PKC pathway, NFκB pathway, Rho/VFIOCK pathway and Ca^2＋ signaling pathway. At the far end of the response, there is evidence for regulation at the level of gene transcription. For example, the production of cell growth factors, transcription factors and osteogenic proteins is enhanced signiflcantly in osteocytes and osteoblasts after FSS stimulation. The precise mechanism involved in mecheno-trensduction and signal transduction remains to be elucidated.