Roles of bone morphogenetic protein type I receptors and smad proteins in osteoblast and chondroblast differentiation
Roles of bone morphogenetic protein type I receptors and smad proteins in osteoblast and chondroblast differentiation
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DOI：
10.1091/mbc.10.11.3801
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发表时间：
1999-11-01
影响因子：
3.3
通讯作者：
Miyazono, K
中科院分区：
文献类型：
--
作者：
Fujii, M;Takeda, K;Miyazono, K
使用基于腺病毒的载体系统检查了 I 型丝氨酸/苏氨酸激酶受体和 Smad 蛋白的生物学效应。骨形态发生蛋白 (BMP) I 型受体（BMPR-IA 和 BMPR-IB；BMPR-I 组）以及激活素受体样激酶 (ALK)-1 和 ALK-2（ALK-1 组）的组成型活性形式可诱导 C2C12 细胞中的碱性磷酸酶活性。作用于 BMP 通路的受体调节 Smads (R-Smads)，例如 Smad1 和 Smad5，也诱导 C2C12 细胞中的碱性磷酸酶活性。 BMP-6 显着增强了 Smad1 或 Smad5 诱导的碱性磷酸酶活性，可能是因为配体触发了 R-Smad 的核转位。抑制性 Smad，即 Smad6 和 Smad7，抑制 BMP-6 或 I 型受体诱导的碱性磷酸酶活性。 ATDC5细胞的软骨分化是由BMPR-I组的受体诱导的，而不是由ALK-1组的受体诱导的。然而，ALK-1 和 BMPR-I 组受体的激酶失活形式阻碍了软骨形成分化。尽管 R-Smads 未能诱导软骨结节形成，但抑制性 Smads 可以阻止它。因此，BMP 诱导的成骨细胞分化主要通过 Smad 信号通路介导，而软骨形成分化可能通过 Smad 依赖性和独立通路传递。
The biological effects of type I serine/threonine kinase receptors and Smad proteins were examined using an adenovirus-based vector system. Constitutively active forms of bone morphogenetic protein (BMP) type I receptors (BMPR-IA and BMPR-IB; BMPR-I group) and those of activin receptor-like kinase (ALK)-1 and ALK-2 (ALK-1 group) induced alkaline phosphatase activity in C2C12 cells. Receptor-regulated Smads (R-Smads) that act in the BMP pathways, such as Smad1 and Smad5, also induced the alkaline phosphatase activity in C2C12 cells. BMP-6 dramatically enhanced alkaline phosphatase activity induced by Smad1 or Smad5, probably because of the nuclear translocation of R-Smads triggered by the ligand. Inhibitory Smads, i.e., Smad6 and Smad7, repressed the alkaline phosphatase activity induced by BMP-6 or the type I receptors. Chondrogenic differentiation of ATDC5 cells was induced by the receptors of the BMPR-I group but not by those of the ALK-1 group. However, kinase-inactive forms of the receptors of the ALK-1 and BMPR-I groups blocked chondrogenic differentiation. Although R-Smads failed to induce cartilage nodule formation, inhibitory Smads blocked it. Osteoblast differentiation induced by BMPs is thus mediated mainly via the Smad-signaling pathway, whereas chondrogenic differentiation may be transmitted by Smad-dependent and independent pathways.