RRC ID 68487
Author Katagiri T, Akiyama S, Namiki M, Komaki M, Yamaguchi A, Rosen V, Wozney JM, Fujisawa-Sehara A, Suda T.
Title Bone morphogenetic protein-2 inhibits terminal differentiation of myogenic cells by suppressing the transcriptional activity of MyoD and myogenin.
Journal Exp Cell Res
Abstract 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 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 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, but 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.
Volume 230(2)
Pages 342-51
Published 1997-2-1
DOI 10.1006/excr.1996.3432
PII S0014-4827(96)93432-1
PMID 9024793
MeSH 3T3 Cells Animals Bone Morphogenetic Protein 2 Bone Morphogenetic Proteins / pharmacology* CHO Cells Cell Differentiation / drug effects* Cell Line Creatine Kinase / genetics Cricetinae Enhancer Elements, Genetic Humans Mice MyoD Protein / genetics* MyoD Protein / metabolism Myogenin / genetics* Myogenin / metabolism Recombinant Fusion Proteins / pharmacology Recombinant Proteins Transcription, Genetic / drug effects* Transforming Growth Factor beta*
IF 3.383
Human and Animal Cells 10T1/2(RCB0247)