Parathyroid hormone-related peptide interacts with bone morphogenetic protein 2 to increase osteoblastogenesis and decrease adipogenesis in pluripotent C3H10T1/2 mesenchymal cells
Parathyroid hormone-related peptide interacts with bone morphogenetic protein 2 to increase osteoblastogenesis and decrease adipogenesis in pluripotent C3H10T1/2 mesenchymal cells
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DOI：
10.1210/en.2003-0273
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发表时间：
2003-12-01
期刊：
影响因子：
4.8
通讯作者：
Goltzman, D
中科院分区：
文献类型：
--
作者：
Chan, GK;Miao, DS;Goltzman, D
我们研究了PTH相关肽（PTHrP）对多能间充质细胞系C3 H10 T1/2中脂肪生成和成骨细胞生成的调节作用。这些细胞表达1型PTH/PTHrP受体，从而允许PTHrP抑制骨形态发生蛋白2（BMP 2）增强过氧化物酶体增殖物激活受体γ和脂肪细胞特异性蛋白aP 2的基因表达以及增加脂质的积累。在BMP 2的存在下，PTHrP或蛋白激酶C（PKC）刺激剂（佛波酯）增加成骨细胞表型的指数的表达，包括碱性磷酸酶，I型胶原和骨钙蛋白，而PKC抑制剂（氯化白屈菜红蛋白）抑制PTHrP的作用。PTHrP和佛波酯增加了BMP 1A受体的基因表达，并且都增强了信号分子SMAD 6的启动子活性的BMP 2依赖性增加。BMP IA受体的过表达促进了BMP 2在PTHrP不存在下增加成骨细胞生成的能力，并且显性负性BMP IA受体变体抑制了BMP 2的这种作用。这些结果表明，PTHrP可以指导成骨细胞，而不是脂肪形成，间充质细胞的承诺，牵连PKC信号在这种活动，并显示PTHrP的作用涉及增强的基因表达的BMP 1A受体，这有利于BMP 2的作用，在增强成骨细胞在多能间充质细胞。
We examined the effect of PTH-related peptide (PTHrP) on modulating adipogenesis and osteoblastogenesis in the pluripotent mesenchymal cell line C3H10T1/2. These cells express the type 1 PTH/PTHrP receptor, thereby allowing PTHrP to inhibit bone morphogenetic protein 2 (BMP2) from enhancing gene expression of peroxisome proliferator-activated receptor gamma and the adipocyte-specific protein aP2 and from augmenting the accumulation of lipid. In the presence of BMP2, PTHrP or a protein kinase C (PKC) stimulator (phorbol ester) increased the expression of indexes of the osteoblast phenotype, including alkaline phosphatase, type I collagen, and osteocalcin, whereas a PKC inhibitor (chelerythrin chloride) inhibited PTHrP action. PTHrP and a phorbol ester increased gene expression of the BMP IA receptor, and both enhanced BMP2-dependent increases in promoter activity of the signaling molecule SMAD6. Overexpression of the BMP IA receptor facilitated the capacity of BMP2 to increase osteoblastogenesis in the absence of PTHrP and a dominant negative BMP IA receptor variant inhibited this effect of BMP2. These results demonstrate that PTHrP can direct osteoblastic, rather then adipogenic, commitment of mesenchymal cells, implicate PKC signaling in this activity, and show that PTHrP action involves enhanced gene expression of the BMP IA receptor, which facilitates BMP2 action in enhancing osteoblastogenesis in pluripotent mesenchymal cells.