《生命科学》 2014, 26(3): 314-318
摘 要:骨质疏松症是由于骨重建过程中骨形成和骨吸收失平衡导致骨总量丢失所致,与成骨细胞分化密切相关。Hippo 通路影响着哺乳动物体内细胞增殖、分化和凋亡过程。Wnt/β-catenin 通路在成骨细胞分化中扮演重要角色。Hippo 下游的靶基因转录共激活因子TAZ 脱磷酸化后具有促进骨髓基质干细胞(BMSCs)向成骨细胞分化,调节成骨特异基因骨钙素表达,调节骨、肾发育,激活Wnt/β-catenin 通路转录反应的功能;而激活的Wnt/β-catenin 通路能通过抑制β-catenin 降解进而抑制TAZ 的降解。因此,TAZ 与Wnt/β-catenin通路相互调控。但是,对TAZ 与Wnt/β-catenin 通路串话是否影响BMSCs 成骨能力尚不清楚。因此,深入研究TAZ 介导的Wnt/β-catenin 通路在骨代谢中的作用,将为深入了解骨质疏松的发病机制具有重要意义。
Abstract: Osteoporosis, which leads to loss of total bone mass in the process of bone remodeling, is due to the imbalance between bone formation and bone resorption and is closely related to the differentiation of osteoblasts. The Hippo pathway affects cell proliferation, differentiation, and the process of apoptosis in mamals. Wnt/β-catenin pathway plays an important role in the osteoblast differentiation. Studies have shown that Hippo downstream target gene transcription coactivator TAZ is able to respectively promote the differentiation of bone marrow stromal cells (BMSCs) to osteoblast, regulate the osteoblast expression of the specific gene osteocalcin, regulate the growth of bone and kidney, and activate transcription reaction of Wnt/β-catenin pathway. And activation of Wnt/β-catenin pathway inhibits TAZ phosphorylation by controlling β-catenin degradation. Therefore, TAZ and Wnt/β-catenin pathway regulate each other mutually. However, there is no clear report about whether crosstalk between TAZ and Wnt/β-catenin pathway can affect the osteogenic ability of BMSCs. Therefore, it is important that studying the roles of TAZ-mediated Wnt/β-catenin pathway in bone metabolism will help us further understand the pathogenesis of osteoporosis.