Parathyroid hormone enhances early and suppresses late stages of osteogenic and chondrogenic development in a BMP-dependent mesenchymal differentiation system (C3H10T1/2)
Parathyroid hormone enhances early and suppresses late stages of osteogenic and chondrogenic development in a BMP-dependent mesenchymal differentiation system (C3H10T1/2)
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DOI：
10.1359/jbmr.1997.12.12.1993
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发表时间：
1997-12-01
影响因子：
6.2
通讯作者：
Gross, G
中科院分区：
文献类型：
--
作者：
Hollnagel, A;Ahrens, M;Gross, G
本研究通过在骨髓间充质祖细胞中重组表达骨形态发生蛋白（BMP），研究了甲状旁腺激素（PTH）对骨/软骨发育的作用（C3 H10 T1/2），PTH/PTH相关蛋白受体在该系统中的组成型表达导致软骨和成骨发育的显著刺激，而配体PTH（1-34）的永久应用通过刺激骨/软骨形成发育的早期和抑制晚期而导致相反的反应。因此，PTH（1-34）对骨形成和软骨细胞发育的这些对比作用似乎取决于细胞的分化状态，成骨和软骨细胞分化潜力在组织学上得到证实，并通过标记基因如c-fos、碱性磷酸酶、骨钙素、胶原蛋白α（1）（I）和胶原蛋白α（1）（II）的遗传分析得到证实。调节成骨和软骨形成发育的能力位于PTH分子的氨基末端（1-34）区域，并且似乎由环磷酸腺苷信号级联介导。其他PTH结构域如PTH（28-48）和PTH（53-84）的应用没有表现出显著的响应，PTH作为间充质发育中的必需因子，控制分化成成骨或软骨谱系的速率，PTH在该系统中的作用的分析证明了重组间充质祖细胞在骨/软骨形成发育的体外分析中的价值。
The role of parathyroid hormone (PTH) upon osteo-/chondrogenic development was investigated in a bone morphogenetic protein (BMP)-dependent differentiation system involving the recombinant expression of BMPs in mesenchymal progenitor cells (C3H10T1/2), The constitutive expression of the PTH/PTH related protein receptor in this system led to a marked stimulation of chondrogenic and osteogenic development, while the permanent application of the ligand PTH(1-34) resulted in opposite responses by stimulating the early and suppressing the late stages of osteo-/chondrogenic development, These contrasting effects of PTH(1-34) on osteogenic and chondrocytic development seem, therefore, to depend on the cellular state of differentiation, The osteogenic and chondrocytic differentiation potential was substantiated histologically and by genetic analyses of marker genes like c-fos, alkaline phosphatase, osteocalcin, collagen alpha(1)(I), and collagen alpha(1)(II). The capacity to regulate osteogenic and chondrogenic development is located in the amino-terminal (1-34) region of the PTH molecule and seems to be mediated by the cyclic adenosine monophosphate signaling cascade, The application of other PTH domains like PTH(28-48) and PTH(53-84) did not exhibit significant responses,]PTH acts as an essential factor in mesenchymal development controlling rates of differentiation into the osteogenic or chondrogenic lineage, The analysis of PTH effects in this system demonstrates the value of recombinant mesenchymal progenitor cells in the in vitro analysis of osteo-/chondrogenic development.