Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada.
J Biol Chem. 2012 Oct 19;287(43):36222-8. doi: 10.1074/jbc.M112.382275. Epub 2012 Aug 28.
Growth plate chondrocytes undergo a coordinated process of differentiation, regulating long bone growth. Parathyroid hormone-like hormone (Pthlh) inhibits hypertrophic differentiation in the growth plate chondrocytes and reduces Hedgehog (Hh) signaling. In mice lacking the Hh mediator Suppressor of fused (Sufu), Pthlh treatment resulted in the up-regulation of Hh activity and an increased number of hypertrophic chondrocytes. Furthermore, Pthlh increased Sufu protein levels, and in chondrocytes lacking Sufu, it was unable to process Hh-regulated Gli transcription factors. Pthlh regulates chondrocyte differentiation and Gli activity in a Sufu-dependent manner, with Sufu acting as a molecular switch in its regulation of differentiation.
生长板软骨细胞经历一个协调的分化过程,调节长骨生长。甲状旁腺激素样激素(Pthlh)抑制生长板软骨细胞的肥大分化,并降低 Hedgehog(Hh)信号。在缺乏 Hedgehog 介体融合抑制因子(Sufu)的小鼠中,Pthlh 处理导致 Hh 活性上调和肥大软骨细胞数量增加。此外,Pthlh 增加了 Sufu 蛋白水平,并且在缺乏 Sufu 的软骨细胞中,它无法处理 Hh 调节的 Gli 转录因子。Pthlh 以 Sufu 依赖的方式调节软骨细胞分化和 Gli 活性,Sufu 作为其分化调节中的分子开关。