Bone morphogenetic protein-2 inhibits terminal differentiation of myogenic cells by suppressing the transcriptional activity of MyoD and myogenin
Bone morphogenetic protein-2 inhibits terminal differentiation of myogenic cells by suppressing the transcriptional activity of MyoD and myogenin
复制标题
DOI：
10.1006/excr.1996.3432
复制
发表时间：
1997-02-01
影响因子：
3.7
通讯作者：
Suda, T
中科院分区：
文献类型：
--
作者：
Katagiri, T;Akiyama, S;Suda, T
骨形态发生蛋白（BMP）是一个细胞因子家族，当植入肌肉组织时诱导异位骨形成。我们报道了BMP-2抑制C2 C12成肌细胞的终末分化，并使它们变成成骨细胞谱系细胞（Katagiri，T.，山口，A.，Komaki，M.，Abe，E.，Takahashi，N.，布雷达，T.，罗森，Wozney，J. M.，Fujisawa-Sehara，A.，和苏达，T.等（1994）J. Cell Biol.121，1755-1766）。在本研究中，我们研究了BMP-2对肌原细胞终末分化的抑制作用的分子机制。当MyoD或肌细胞生成素cDNA被引入C3 H10 T1/2（10 T1/2）细胞中时，含有四个拷贝的肌肉肌酸激酶（MCK）增强子的右E-box的肌肉特异性CAT报告基因，CAT活性被BMP-2剂量依赖性地抑制。此外，BMP-2抑制这些稳定表达MyoD或肌细胞生成素的亚克隆10 T1/2细胞向表达肌球蛋白重链和肌钙蛋白T的成熟肌管的终末分化。亚克隆的MyoD转染的NIH 3 T3细胞分化成成熟的肌肉细胞也受到BMP-2的抑制。BMP-2在10 T1/2来源的MyoD转染细胞中诱导碱性磷酸酶活性，而在NIH 3 T3来源的MyoD转染细胞中不诱导碱性磷酸酶活性。这些细胞组成型表达外源性MyoD和肌细胞生成素，其仅定位于细胞核中，而不管BMP-2的存在和不存在。然而，当与BMP-2培养时，这些细胞未能表达内源性肌生成因子和MCK的mRNA。在使用肌细胞核提取物的电泳迁移率变动分析中，即使在BMP-2存在下，MyoD和肌细胞生成素也与MCK基因增强子区域中的右侧E-box结合。这些结果表明，BMP-2抑制终末分化的成肌细胞通过抑制成肌因子的转录活性。(C)北京：科学出版社.
Bone morphogenetic protein (BMP) is a family of cytokines that induce ectopic bone formation when implanted into muscular tissues. We reported that BMP-2 inhibits the terminal differentiation of C2C12 myoblasts and concerts them into osteoblast lineage cells (Katagiri, T., Yamaguchi, A., Komaki, M., Abe, E., Takahashi, N., Breda, T., Rosen, V., Wozney, J. M., Fujisawa-Sehara, A., and Suda, T. (1994) J. Cell Biol. 121, 1755-1766). In the present study, we examined the molecular mechanism of the inhibitory effect of BMP-2 on terminal differentiation of myogenic cells. When either MyoD or myogenin cDNA was introduced into C3H10T1/2 (10T1/2) cells with a muscle-specific CAT reporter containing four copies of the right E-box of muscle creatine kinase (MCK) enhancer, the CAT activity was dose-dependently suppressed by BMP-2. Furthermore, BMP-2 inhibited the terminal differentiation of these subclonal 10T1/2 cells that stably expressed MyoD or myogenin into mature myotubes that expressed myosin heavy chain and troponin T. The differentiation of a subclone of the MyoD-transfected NIH3T3 cells into mature muscle cells was also inhibited by BMP-2. BMP-2 induced alkaline phosphatase activity in 10T1/2-derived, hut not in NIH3T3-derived MyoD-transfected cells. These cells constitutively expressed exogenous MyoD and myogenin, which were localized exclusively in the nuclei irrespective of the presence and the absence of BMP-2. However, these cells failed to express the mRNAs of endogenous myogenic factors and MCK when cultured with BMP-2. In the electrophoresis mobility shift assay using nuclear extracts of the myogenic cells, MyoD and myogenin bound to the right E-box in the enhancer region of the MCK gene even in the presence of BMP-2. These results suggest that BMP-2 inhibits the terminal differentiation of myogenic cells by suppressing the transcriptional activity of the myogenic factors. (C) 1997 Academic Press.