Suppressor of Fused (Sufu) Mediates the Effect of Parathyroid Hormone-like Hormone (Pthlh) on Chondrocyte Differentiation in the Growth Plate
Suppressor of Fused (Sufu) Mediates the Effect of Parathyroid Hormone-like Hormone (Pthlh) on Chondrocyte Differentiation in the Growth Plate
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DOI：
10.1074/jbc.m112.382275
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发表时间：
2012-10-19
影响因子：
4.8
通讯作者：
Alman, Benjamin A.
中科院分区：
文献类型：
--
作者：
Hsu, Shu-Hsuan C.;Zhang, Xiaoyun;Alman, Benjamin A.
生长板软骨细胞经历协调的分化过程，调节长骨生长。甲状旁腺素样激素（Pthlh）抑制生长板软骨细胞的肥大分化并减少Hedgehog（Hh）信号传导。在缺乏融合的Hh介质抑制剂（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在其分化调节中充当分子开关。
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.