Smad1 and Smad5 act downstream of intracellular signalings of BMP-2 that inhibits myogenic differentiation and induces osteoblast differentiation in C2C12 myoblasts
Smad1 and Smad5 act downstream of intracellular signalings of BMP-2 that inhibits myogenic differentiation and induces osteoblast differentiation in C2C12 myoblasts
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DOI：
10.1006/bbrc.1997.7325
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发表时间：
1997-09-18
影响因子：
3.1
通讯作者：
Suda, T
中科院分区：
文献类型：
--
作者：
Yamamoto, N;Akiyama, S;Suda, T
骨形态发生蛋白-α（BMP-2）抑制C2 C12成肌细胞的终末分化并将它们转化成成骨细胞谱系细胞（Katagiri，T.，山口，A.，Komaki，M.，Abe，E.，高桥，N.，Ikeda，T.，罗森，Wozney，J.M.，Fujisawa-Sehara，A.，和苏达T.等（1994）J. Cell Biol.127，1755-1766）。在本研究中，我们研究了可能参与的Smad蛋白，脊椎动物同源的果蝇母亲对decapentaplegic，在BMP对C2 C12成肌细胞的分化的影响。C2 C12细胞表达Smad 1、Smad 2、Smad 4和Smad 5 mRNA，并且表达水平未被BMP-2或TGF-β 1处理改变。当Smads瞬时转染到C2 C12细胞中时，Smad 1和Smad 5均诱导碱性磷酸酶（ALP）活性，并在无BMP-2的情况下降低肌细胞生成素启动子/氯霉素乙酰转移酶（myogenin-CAT）的活性。当C-末端截短的Smad 1和Smad 5转染到组成型活性BMP受体IB型（BMPR-IB）表达C2 C12细胞中时，BMP信号被阻断，导致肌生成素-CAT活性增加。另一方面，Smad 1和Smad 5在MyoD转染的NIH 3 T3成纤维细胞中降低肌细胞生成素-CAT活性，但不诱导ALP活性。这些结果表明，Smad 1和Smad 5都参与了细胞内BMP信号，抑制肌源性分化和诱导成骨细胞分化的C2 C12细胞，这两个分化途径的转换是独立的调节在转录水平。(C)北京：科学出版社.
Bone morphogenetic protein-a (BMP-2) inhibits terminal differentiation of C2C12 myoblasts and converts them into osteoblast lineage cells (Katagiri, T., Yamaguchi, A., Komaki, M., Abe, E., Takahashi, N., Ikeda, T., Rosen, V., Wozney, J.M., Fujisawa-Sehara, A., and Suda T. (1994) J. Cell Biol. 127, 1755-1766). In the present study, we examined the possible involvement of Smad proteins, vertebrate homologues of Drosophila Mothers against decapentaplegic, in the BMP effects on the differentiation of C2C12 myoblasts. C2C12 cells expressed Smad1, Smad2, Smad4, and Smad5 mRNAs, and expression levels were not altered by treatment with BMP-2 or TGF-beta 1. When Smads were transiently transfected into C2C12 cells, both Smad1 and Smad5 induced alkaline phosphatase (ALP) activity and decreased the activity of myogenin promoter/chloramphenicol acetyltransferase (myogenin-CAT) without BMP-2. When C-terminal-truncated Smad1 and Smad5 were transfected into constitutively active BMP receptor type IB (BMPR-IB)-expressing C2C12 cells, BMP signals were blocked, resulting in an increase in myogenin-CAT activity. On the other hand, Smad1 and Smad5 decreased myogenin-CAT activity but did not induce ALP activity in MyoD-transfected NIH3T3 fibroblasts. These results suggest that both Smad1 and Smad5 are involved in the intracellular BMP signals which inhibit myogenic differentiation and induce osteoblast differentiation in C2C12 cells, and that the conversion of the two differentiation pathways is regulated independently at a transcriptional level. (C) 1997 Academic Press.