Myostatin, a Negative Regulator of Muscle Growth, Functions by Inhibiting Myoblast Proliferation*

By Mark Thomas, Brett C. Langley, C. Berry, Mridula Sharma, S. Kirk, J. Bass, R. Kambadur. Journal of Biological Chemistry, 2000

1,067 citations recorded by the source corpus.

Myostatin, a member of the transforming growth factor-β (TGF-β) superfamily, has been shown to be a negative regulator of myogenesis. Here we show that myostatin functions by controlling the proliferation of muscle precursor cells. When C2C12 myoblasts were incubated with myostatin, proliferation of myoblasts decreased with increasing levels of myostatin. Fluorescence-activated cell sorting analysis revealed that myostatin prevented the progression of myoblasts from the G1- to S-phase of the cell cycle. Western analysis indicated that myostatin specifically up-regulated p21Waf1, Cip1, a cyclin-dependent kinase inhibitor, and decreased the levels and activity of Cdk2 protein in myoblasts. Furthermore, we also observed that in myoblasts treated with myostatin protein, Rb was predominately present in the hypophosphorylated form. These results suggests that, in response to myostatin signaling, there is an increase in p21 expression and a decrease in Cdk2 protein and activity thus resulting in an accumulation of hypophosphorylated Rb protein. This, in turn, leads to the arrest of myoblasts in G1-phase of cell cycle. Thus, we propose that the generalized muscular hyperplasia phenotype observed in animals that lack functional myostatin could be as a result of deregulated myoblast proliferation.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/1d23c762e638a24e032fb334a031fafce76bc3ab

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In Molecular Biology

1. Sophie B. P. Chargé
2. J. Zambonino-Infante
3. Michael A. Rudnicki
4. Carlos D. Bustamante

Citations in the corpus

• Myostatin negatively regulates satellite cell activation and self-renewal (2003, methodology): “Primary and secondary myoblasts that lack Myostatin proliferate faster Previously, we have shown that high concentrations of Myostatin inhibit the proliferation of myoblasts by controlling the G 1 to S transition during cell cycle (Thomas et al., 2000).”
• Enhancement of meat production by environmental manipulations in embryo and young broilers (2006, background): “Myostatin is a member of the transforming growth factor-beta (TGF-β) super-family that inhibits satellite cell proliferation and differentiation (Thomas et al., 2000; Joulia et al., 2003) by World’s Poultry Science Journal, Vol. 62, September 2006 489 maintaining them in their quiescent state…”
• Cellular and molecular regulation of muscle regeneration. (2004, background): “Furthermore, recent in vitro experiments demonstrated that at high levels, MSTN inhibits proliferation and affects differentiation of C2C12, via cyclin-Cdk2 inactivation of retinoblastoma protein (Rb) (253, 254, 309, 313).”
• Fantastically plastic: fish larvae equipped for a new world (2013, background): “1), S224–S267 © 2013 Wiley Publishing Asia Pty Ltd S249 growth and development, by inhibiting specifically myoblast proliferation via cell-cycle arrest (Thomas et al. 2000).”
• A Mutation in the Myostatin Gene Increases Muscle Mass and Enhances Racing Performance in Heterozygote Dogs (2007, background): “therefore controls the total number of muscle fibers by regulating overall myoblast proliferation [”