Limits...
Myostatin negatively regulates satellite cell activation and self-renewal.

McCroskery S, Thomas M, Maxwell L, Sharma M, Kambadur R - J. Cell Biol. (2003)

Bottom Line: BrdU labeling in vivo revealed that, among the Myostatin-deficient satellite cells, higher numbers of satellite cells are activated as compared with wild type.Cell cycle analysis confirms that Myostatin up-regulated p21, a Cdk inhibitor, and decreased the levels and activity of Cdk2 protein in satellite cells.Taken together, these results suggest that Myostatin is a potent negative regulator of satellite cell activation and thus signals the quiescence of satellite cells.

View Article: PubMed Central - PubMed

Affiliation: Animal Genomics, AgResearch, Hamilton 2015, New Zealand.

ABSTRACT
Satellite cells are quiescent muscle stem cells that promote postnatal muscle growth and repair. Here we show that myostatin, a TGF-beta member, signals satellite cell quiescence and also negatively regulates satellite cell self-renewal. BrdU labeling in vivo revealed that, among the Myostatin-deficient satellite cells, higher numbers of satellite cells are activated as compared with wild type. In contrast, addition of Myostatin to myofiber explant cultures inhibits satellite cell activation. Cell cycle analysis confirms that Myostatin up-regulated p21, a Cdk inhibitor, and decreased the levels and activity of Cdk2 protein in satellite cells. Hence, Myostatin negatively regulates the G1 to S progression and thus maintains the quiescent status of satellite cells. Immunohistochemical analysis with CD34 antibodies indicates that there is an increased number of satellite cells per unit length of freshly isolated Mstn-/- muscle fibers. Determination of proliferation rate suggests that this elevation in satellite cell number could be due to increased self-renewal and delayed expression of the differentiation gene (myogenin) in Mstn-/- adult myoblasts. Taken together, these results suggest that Myostatin is a potent negative regulator of satellite cell activation and thus signals the quiescence of satellite cells.

Show MeSH

Related in: MedlinePlus

A model for the role of Myostatin in postnatal muscle growth. Quiescent satellite cells on muscle fibers are activated in response to muscle injury to give rise to myoblasts. Proliferating myoblasts can either fuse with the existing fiber or differentiate into a nascent myotube. A portion of proliferating myoblasts, however, can revert to become quiescent satellite cells, thus resulting in self-renewal. As Myostatin is a negative regulator of cell cycle progression, high levels of Myostatin in satellite cells block the activation to maintain quiescence.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2172861&req=5

fig8: A model for the role of Myostatin in postnatal muscle growth. Quiescent satellite cells on muscle fibers are activated in response to muscle injury to give rise to myoblasts. Proliferating myoblasts can either fuse with the existing fiber or differentiate into a nascent myotube. A portion of proliferating myoblasts, however, can revert to become quiescent satellite cells, thus resulting in self-renewal. As Myostatin is a negative regulator of cell cycle progression, high levels of Myostatin in satellite cells block the activation to maintain quiescence.

Mentions: In conclusion, we propose that Myostatin blocks the activation of satellite cells and also negatively regulates self-renewal of satellite cells (Fig. 8). Increased activation of Mstn−/− satellite cells, and subsequent enhanced proliferation with delayed differentiation of myostatin- myoblasts, could thus be the primary reason for the increased postnatal muscle growth and hypertrophy in myostatin- animals. To our knowledge, this is the first report of a secreted growth factor that is expressed in satellite cells and maintains the satellite cell quiescence.


Myostatin negatively regulates satellite cell activation and self-renewal.

McCroskery S, Thomas M, Maxwell L, Sharma M, Kambadur R - J. Cell Biol. (2003)

A model for the role of Myostatin in postnatal muscle growth. Quiescent satellite cells on muscle fibers are activated in response to muscle injury to give rise to myoblasts. Proliferating myoblasts can either fuse with the existing fiber or differentiate into a nascent myotube. A portion of proliferating myoblasts, however, can revert to become quiescent satellite cells, thus resulting in self-renewal. As Myostatin is a negative regulator of cell cycle progression, high levels of Myostatin in satellite cells block the activation to maintain quiescence.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172861&req=5

fig8: A model for the role of Myostatin in postnatal muscle growth. Quiescent satellite cells on muscle fibers are activated in response to muscle injury to give rise to myoblasts. Proliferating myoblasts can either fuse with the existing fiber or differentiate into a nascent myotube. A portion of proliferating myoblasts, however, can revert to become quiescent satellite cells, thus resulting in self-renewal. As Myostatin is a negative regulator of cell cycle progression, high levels of Myostatin in satellite cells block the activation to maintain quiescence.
Mentions: In conclusion, we propose that Myostatin blocks the activation of satellite cells and also negatively regulates self-renewal of satellite cells (Fig. 8). Increased activation of Mstn−/− satellite cells, and subsequent enhanced proliferation with delayed differentiation of myostatin- myoblasts, could thus be the primary reason for the increased postnatal muscle growth and hypertrophy in myostatin- animals. To our knowledge, this is the first report of a secreted growth factor that is expressed in satellite cells and maintains the satellite cell quiescence.

Bottom Line: BrdU labeling in vivo revealed that, among the Myostatin-deficient satellite cells, higher numbers of satellite cells are activated as compared with wild type.Cell cycle analysis confirms that Myostatin up-regulated p21, a Cdk inhibitor, and decreased the levels and activity of Cdk2 protein in satellite cells.Taken together, these results suggest that Myostatin is a potent negative regulator of satellite cell activation and thus signals the quiescence of satellite cells.

View Article: PubMed Central - PubMed

Affiliation: Animal Genomics, AgResearch, Hamilton 2015, New Zealand.

ABSTRACT
Satellite cells are quiescent muscle stem cells that promote postnatal muscle growth and repair. Here we show that myostatin, a TGF-beta member, signals satellite cell quiescence and also negatively regulates satellite cell self-renewal. BrdU labeling in vivo revealed that, among the Myostatin-deficient satellite cells, higher numbers of satellite cells are activated as compared with wild type. In contrast, addition of Myostatin to myofiber explant cultures inhibits satellite cell activation. Cell cycle analysis confirms that Myostatin up-regulated p21, a Cdk inhibitor, and decreased the levels and activity of Cdk2 protein in satellite cells. Hence, Myostatin negatively regulates the G1 to S progression and thus maintains the quiescent status of satellite cells. Immunohistochemical analysis with CD34 antibodies indicates that there is an increased number of satellite cells per unit length of freshly isolated Mstn-/- muscle fibers. Determination of proliferation rate suggests that this elevation in satellite cell number could be due to increased self-renewal and delayed expression of the differentiation gene (myogenin) in Mstn-/- adult myoblasts. Taken together, these results suggest that Myostatin is a potent negative regulator of satellite cell activation and thus signals the quiescence of satellite cells.

Show MeSH
Related in: MedlinePlus