Role of Muscle Stem Cells During Skeletal Regeneration
Abstract
Although the importance of muscle in skeletal regeneration is well recognized clinically, the mechanisms by which muscle supports bone repair have remained elusive. Muscle flaps are often used to cover the damaged bone after traumatic injury yet their contribution to bone healing is not known. Here, we show that direct bone-muscle interactions are required for periosteum activation and callus formation, and that muscle grafts provide a source of stem cells for skeletal regeneration. We investigated the role of satellite cells, the muscle stem cells. Satellite cells loss in Pax7−/− mice and satellite cell ablation in Pax7CreERT2/+;DTAf/f mice impaired bone regeneration. Although satellite cells did not contribute as a large source of cells endogenously, they exhibited a potential to contribute to bone repair after transplantation. The fracture healing phenotype in Pax7CreERT2/+;DTAf/f mice was associated with decreased bone morphogenetic proteins (BMPs), insulin-like growth factor 1, and fibroblast growth factor 2 expression that are normally upregulated in response to fracture in satellite cells. Exogenous rhBMP2 improved bone healing in Pax7CreERT2/+;DTAf/f mice further supporting the role of satellite cells as a source of growth factors. These results provide the first functional evidence for a direct contribution of muscle to bone regeneration with important clinical implications as it may impact the use of muscle flaps, muscle stem cells, and growth factors in orthopedic applications. Stem Cells 2015;33:1501–1511
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Satellite cells are essential for the regeneration of skeletal muscle after injury.
“Studies with these mice showed that satellite cells are essential for the regeneration of skeletal muscle after injury (2, 81, 107),”
From The Hippo signal transduction network for exercise physiologists (2016) · cites this paper as [2]
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References 51 · Cited by 78
- Authors
- Abou-Khalil, R., Yang, F., Lieu, S., Julien, A., Perry, J., Pereira, C., Relaix, F., Miclau, T., Marcucio, R., & Colnot, C.
- Affiliations
- Hôpital Necker-Enfants Malades (FR)
- San Francisco General Hospital (US)
- INSERM UMR1163 Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Hôpital Necker Enfants Malades, Paris, France
- Inserm (FR)
- Corresponding author
- Colnot, Céline
- Venue
- Stem Cells
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-04-23
- Volume
- 33
- Issue
- 5
- Pages
- 1501-1511
- ISSN
- 1066-5099 (ISSN-L)
- 1549-4918
- OpenAlex
- W1854707721
- Cited by
- 78
- References
- 51
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 7 · 2023: 6 · 2022: 4 · 2021: 6 · 2020: 14 · 2019: 8 · 2018: 9 · 2017: 13 · 2016: 5 · 2015: 2
- FWCI
- 4.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Stem Cells (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (1011717)
- Sanofi
- Osteosynthesis and Trauma Care Foundation (2011-CCSP, ANR-13-BSV1-001-01)
- Institut des maladies génétiques Imagine
- European Commission (268227)
- Agence Nationale de la Recherche (ANR-13-BSV1-0001, ANR- 13-BSV1-001)
- Institut National de la Santé et de la Recherche Médicale
- National Institutes of Health
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR057344, AR057344)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Epidemiology › Bone fractures and treatments
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Keywords
- muscle stem cells, satellite cells, skeletal regeneration, bone regeneration, fracture healing, muscle-bone interaction, callus formation, muscle flap, Pax7, bone morphogenetic proteins, insulin-like growth factor I, fibroblast growth factor 2, growth factors, muscle grafts
- MeSH terms
- Animals, Bone and Bones, Bony Callus, Humans, Mice, Inbred C57BL, Periosteum, Regeneration, Stem Cells, Muscle, Skeletal, Myoblasts, Satellite Cells, Skeletal Muscle
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