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Cited by 784Muscle Physiology and DisordersTGF-β signaling in diseasesNeurogenetic and Muscular Disorders Research

The DOI matches its Crossref record; 43 of the 44 references it cites were found in a registry or an index.

Myostatin negatively regulates satellite cell activation and self-renewal

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McCroskery, Seumas, Thomas, Mark, Maxwell, Linda, Sharma, Mridula, Kambadur, Ravi·2003·The Journal of Cell Biology
DOI 10.1083/jcb.200207056PMC PMC2172861
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Abstract

Satellite cells are quiescent muscle stem cells that promote postnatal muscle growth and repair. Here we show that myostatin, a TGF-β 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.

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  1. 1989, Med. Sci. Sports Exerc., 21, S164
  2. 1999, Am. J. Physiol., 277, R601
  3. 1993, Mol. Cell Biol. Hum. Dis. Ser., 3, 210
  4. 1997, Methods Mol. Biol., 75, 131

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Metadata

Authors
McCroskery, S., Thomas, M., Maxwell, L., Sharma, M., & Kambadur, R.
Affiliations
  • University of Auckland (NZ)
  • AgResearch (NZ)
Corresponding author
Kambadur, Ravi
ORCID
Thomas, Mark
Venue
The Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2003-09-08
Volume
162
Issue
6
Pages
1135-1147
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.200207056
PMC
PMC2172861
OpenAlex
W2048134135
Cited by
784
References
44
Citations by year
2026: 20 · 2025: 20 · 2024: 22 · 2023: 17 · 2022: 25 · 2021: 32 · 2020: 26 · 2019: 25 · 2018: 33 · 2017: 28 · 2016: 42 · 2015: 38 · 2014: 54 · 2013: 54 · 2012: 48
FWCI
11.05
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Cell Biology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Health Sciences › Medicine › Genetics (clinical) › Neurogenetic and Muscular Disorders Research
Keywords
myostatin, satellite cells, muscle stem cells, quiescence, self-renewal, satellite cell activation, p21, CDK2, G1/S cell cycle progression, myogenesis, myogenin, Mstn knockout mice, TGF-beta signaling
MeSH terms
Animals, Cell Differentiation, Cell Division, Regeneration, Down-Regulation, Up-Regulation, G1 Phase, S Phase, Transforming Growth Factor beta, Cyclins, Protein Serine-Threonine Kinases, Myogenin, Mice, Knockout, Muscle, Skeletal, Muscle Fibers, Skeletal, Gene Expression Regulation, Developmental, Cyclin-Dependent Kinases, Antigens, CD34, Feedback, Physiological, Myoblasts, Satellite Cells, Skeletal Muscle, CDC2-CDC28 Kinases, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinase 2, Mice, Myostatin

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