PTH/PTHrP receptor in early development and Indian hedgehog-regulated bone growth
PTH/PTHrP receptor in early development and Indian hedgehog-regulated bone growth
复制标题
DOI：
10.1126/science.273.5275.663
复制
发表时间：
1996-08-02
期刊：
影响因子：
56.9
通讯作者：
Kronenberg, HM
中科院分区：
文献类型：
--
作者：
Lanske, B;Karaplis, AC;Kronenberg, HM
PTH/PTHrP受体与两种具有不同功能的配体结合：钙调节激素，甲状旁腺激素（PTH）和旁分泌因子，PTH相关蛋白（PTHrP）。每个配体反过来可能激活一个以上的受体。PTH/PTHrP受体的功能通过同源重组删除鼠基因进行研究。大多数PTH/PTHrP受体（-/-）突变小鼠在妊娠中期死亡，这可能是由于母体PTHrP的影响，而在PTHrP（-/-）小鼠中未观察到这种表型。存活的小鼠表现出骨中软骨细胞的加速分化，并且它们的骨在外植体培养中生长，对PTHrP和Sonic hedgehog的作用具有抗性。这些结果表明，PTH/PTHrP受体介导的影响，印度刺猬和PTHrP对软骨细胞分化。
The PTH/PTHrP receptor binds to two ligands with distinct functions: the calcium-regulating hormone, parathyroid hormone (PTH), and the paracrine factor, PTH-related protein (PTHrP). Each ligand, in turn, is likely to activate more than one receptor. The functions of the PTH/PTHrP receptor were investigated by deletion of the murine gene by homologous recombination. Most PTH/PTHrP receptor (-/-) mutant mice died in mid-gestation, a phenotype not observed in PTHrP (-/-) mice, perhaps because of the effects of maternal PTHrP. Mice that survived exhibited accelerated differentiation of chondrocytes in bone, and their bones, grown in explant culture, were resistant to the effects of PTHrP and Sonic hedgehog. These results suggest that the PTH/PTHrP receptor mediates the effects of Indian Hedgehog and PTHrP on chondrocyte differentiation.