Type β Transforming Growth Factor is an Inhibitor of Myogenic Differentiation

We have investigated the effect of type β transforming growth factor (TGF-β ) on the differentiation of skeletal muscle myoblasts. TGF-β potently (ID50≈ 10 pM) prevents established cell lines and primary cultures of rat and chicken embryo myoblasts from fusing into multinucleated myotubes. Inhibitio...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1986-11, Vol.83 (21), p.8206-8210
Main Authors: Massagué, Joan, Cheifetz, Sela, Endo, Takeshi, Nadal-Ginard, Bernardo
Format: Article
Language:English
Subjects:
Biological and medical sciences
Cell Differentiation - drug effects
Cell differentiation, maturation, development, hematopoiesis
Cell Fusion - drug effects
Cell growth
Cell Line
Cell lines
Cell physiology
Cells
Cellular differentiation
Collagen - biosynthesis
Collagens
Creatine Kinase - analysis
Extracellular matrix
Fibronectins - biosynthesis
Fundamental and applied biological sciences. Psychology
Molecular and cellular biology
Muscle fibers
Muscles - cytology
Muscles - drug effects
Muscles - metabolism
Myoblasts
Peptides - pharmacology
Receptors
Receptors, Cell Surface - analysis
RNA, Messenger - analysis
Skeletal muscle
Transforming Growth Factors
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Summary:We have investigated the effect of type β transforming growth factor (TGF-β ) on the differentiation of skeletal muscle myoblasts. TGF-β potently (ID50≈ 10 pM) prevents established cell lines and primary cultures of rat and chicken embryo myoblasts from fusing into multinucleated myotubes. Inhibition of morphological differentiation by TGF-β correlates with inhibition of the expression of muscle-specific mRNAs and proteins, strong induction of extracellular matrix type I collagen and fibronectin, and a marked tendency of the treated myoblasts to aggregate into densely multilayered arrays or clusters. Myogenic differentiation can resume after removal of TGF-β from the medium. Examination of the time of action of TGF-β shows that myoblasts stochastically reach a point beyond which they become insensitive to the inhibitory action of TGF-β . This resistance of committed myoblasts to the inhibitory action of TGF-β is not associated with any measurable change in the number or affinity of TGF-β receptors in those cells. The results indicate that TGF-β is a potent inhibitor of myogenesis and may regulate muscle development in vivo.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.83.21.8206