Hippo信号通路调控骨折愈合的研究进展

Research progress on role of Hippo pathway in bone repair

骨折发生后断端间组织修复程序的启动和运行对于骨折愈合至关重要,该过程经历血肿炎症机化期、原始骨痂期形成期和骨痂改造塑形期等三个相互交织和逐渐演进阶段,并由骨髓腔内多种组织、细胞、细胞因子等参与完成。在研究骨折愈合的机制中发现有许多信号通路及分子调控骨修复,包括骨形成、骨重建以及新生血管形成,而在细胞层面上则是对成骨细胞、软骨细胞、破骨细胞以及内皮细胞的调控。Hippo信号通路是一条维持器官体积大小和细胞增殖与凋亡平衡的信号通路,而在维持骨稳态以及骨代谢中也有着重要作用,在其调控骨发育和修复过程中,通过蛋白激酶级联反应和转录辅助激活因子作用下调控微环境下细胞的生理活动。Hippo信号通路上下游效应分子直接或间接调控骨代谢细胞增殖、分化和凋亡等多个过程,且与Wnt信号通路、Notch信号通路等相关骨修复过程重要通路的交互均表明,Hippo信号通路在调控骨折愈合中发挥着重要的作用,可能成为促进骨折愈合的治疗的新靶点。故综述Hippo信号通路的调节机制以及在骨折愈合过程中发挥调控作用的研究进展,并展望了以其为靶点促进骨愈合的研究前景。

The initiation and operation of the tissue repair program between the broken ends after fracture is very important for fracture healing,which goes through three intertwined and gradual evolution stages:hematoma inflammatory organization stage,primitive callus formation stage and callus remodeling stage.It is completed by a variety of tissues,cells and cytokines in the bone marrow cavity.In the study of the mechanism of fracture healing,it is found that there are many signal pathways and molecules regulating bone repair,including bone formation,bone remodeling and neovascularization.At the cellular level,it regulates osteoblasts,chondrocytes,osteoclasts and endothelial cells.Hippo signaling pathway is a signal pathway that maintains the size of organs and the balance between cell proliferation and apoptosis,and also plays an important role in maintaining bone homeostasis and bone metabolism.In the process of regulating bone development and repair,it regulates the physiological activities of cells in microenvironment through protein kinase cascade reaction and transcriptional coactivator.The upstream and downstream effectors of Hippo signal pathway directly or indirectly regulate the proliferation,differentiation and apoptosis of bone metabolic cells,and the interaction with Wnt signal pathway,Notch signal pathway and other important pathways related to bone repair show that Hippo signal pathway plays an important role in the regulation of fracture healing and may become a new target to promote fracture healing.This article reviews the regulatory mechanism of Hippo signaling pathway and its regulatory role in the process of fracture healing,and looks forward to the research prospect of promoting bone healing by using it as a target.