Basic helix-loop-helix protein DEC1 promotes chondrocyte differentiation at the early and terminal stages
Basic helix-loop-helix protein DEC1 promotes chondrocyte differentiation at the early and terminal stages
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DOI：
10.1074/jbc.m206771200
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发表时间：
2002-12-20
影响因子：
4.8
通讯作者：
Kato, Y
中科院分区：
文献类型：
--
作者：
Shen, M;Yoshida, E;Kato, Y
在ATDC 5细胞和生长板软骨细胞的培养物中，以及在体内生长板软骨中，碱性螺旋-环-螺旋转录因子DEC 1（BHLHB 2）/Stra 13/Sharp 2的mRNA水平在软骨细胞分化过程中上调。在ATDC 5细胞中强制表达DEC 1诱导软骨分化，胰岛素增加了DEC 1过表达的这种作用。甲状旁腺激素（PTH）和PTHrP抑制DEC 1的表达和ATDC 5细胞的分化，但DEC 1过表达拮抗PTH/PTHrP的这种抑制作用。转化生长因子-β或骨形态发生蛋白-2，以及胰岛素，诱导DEC 1在ATDC 5培养物中的表达，其中它诱导软骨形成分化。在暴露于转化生长因子-β和胰岛素的骨髓间充质干细胞的颗粒培养物中，DEC 1在软骨细胞分化的最早阶段和肥大阶段被诱导。在间充质细胞中过表达DEC 1诱导II型胶原、印度刺猬和Runx 2的mRNA表达，以及软骨基质积累;在肥大前期生长板软骨细胞中过表达DEC 1增加印度刺猬、Runx 2和X型胶原的mRNA水平，还增加碱性磷酸酶活性和矿化。据我们所知，DEC 1是第一个既能促进软骨分化又能促进终末分化的转录因子。
The mRNA level of basic helix-loop-helix transcription factor DEC1 (BHLHB2)/Stra13/Sharp2 was up-regulated during chondrocyte differentiation in cultures of ATDC5 cells and growth plate chondrocytes, and in growth plate cartilage in vivo. Forced expression of DEC1 in ATDC5 cells induced chondrogenic differentiation, and insulin increased this effect of DEC1 overexpression. Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) suppressed DEC1 expression and the differentiation of ATDC5 cells, but DEC1 overexpression antagonized this inhibitory action of PTH/PTHrP. Transforming growth factor-beta or bone morphogenetic protein-2, as well as insulin, induced DEC1 expression in ATDC5 cultures where it induced chondrogenic differentiation. In pellet cultures of bone marrow mesenchymal stem cells exposed to transforming growth factor-beta and insulin, DEC1 was induced at the earliest stage of chondrocyte differentiation and also at the hypertrophic stage. Overexpression of DEC1 in the mesenchymal cells induced the mRNA expressions of type II collagen, Indian hedgehog, and Runx2, as well as cartilage matrix accumulation; overexpression of DEC1 in growth plate chondrocytes at the prehypertrophic stage increased the mRNA levels of Indian hedgehog, Runx2, and type X collagen, and also increased alkaline phosphatase activity and mineralization. To our knowledge, DEC1 is the first transcription factor that can promote both chondrogenic differentiation and terminal differentiation.