The PTH/PTHrP receptor can delay chondrocyte hypertrophy in vivo without activating phospholipase C
The PTH/PTHrP receptor can delay chondrocyte hypertrophy in vivo without activating phospholipase C
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DOI：
10.1016/s1534-5807(02)00218-6
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发表时间：
2002-08-01
影响因子：
11.8
通讯作者：
Kronenberg, HM
中科院分区：
文献类型：
--
作者：
Guo, J;Chung, U;Kronenberg, HM
一个G蛋白偶联受体（GPCR）可以激活一个以上的G蛋白，但这种激活的生理重要性尚未在体内得到证实。我们已经产生了小鼠表达专门的突变形式的PTH/PTHrP受体（DSEL），激活腺苷酸环化酶正常，但不磷脂酶C（PLC）。DSEL突变小鼠表现出胚胎软骨内骨发育异常，包括骨化延迟和软骨细胞增殖增加。体外胚胎跖骨分化的分析表明，PTH（1-34）和毛喉素抑制，而活性佛波酯刺激，肥大分化。因此，通过PTH/PTHrP受体的PLC信号传导通常减缓软骨细胞的增殖并加速软骨细胞的分化，这是对抗PTH/PTHrP受体的主导作用并涉及cAMP依赖性信号传导途径的作用。
One G protein-coupled receptor (GPCR) can activate more than one G protein, but the physiologic importance of such activation has not been demonstrated in vivo. We have generated mice expressing exclusively a mutant form of the PTH/PTHrP receptor (DSEL) that activates adenylyl cyclase normally but not phospholipase C (PLC). DSEL mutant mice exhibit abnormalities in embryonic endochondral bone development, including delayed ossification and increased chondrocyte proliferation. Analysis of the differentiation of embryonic metatarsals in vitro shows that PTH(1-34) and forskolin inhibit, whereas active phorbol ester stimulates, hypertrophic differentiation. Thus, PLC signaling via the PTH/PTHrP receptor normally slows the proliferation and hastens the differentiation of chondrocytes, actions that oppose the dominant effects of PTH/PTHrP receptors and that involve cAMP-dependent signaling pathways.