BMP signalling permits population expansion by preventing premature myogenic differentiation in muscle satellite cells

Satellite cells are the resident stem cells of adult skeletal muscle, supplying myonuclei for homoeostasis, hypertrophy and repair. In this study, we have examined the role of bone morphogenetic protein (BMP) signalling in regulating satellite cell function. Activated satellite cells expressed BMP r...

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Veröffentlicht in:Cell death and differentiation 2011-02, Vol.18 (2), p.222-234
Hauptverfasser: Ono, Y, Calhabeu, F, Morgan, J E, Katagiri, T, Amthor, H, Zammit, P S
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container_issue 2
container_start_page 222
container_title Cell death and differentiation
container_volume 18
creator Ono, Y
Calhabeu, F
Morgan, J E
Katagiri, T
Amthor, H
Zammit, P S
description Satellite cells are the resident stem cells of adult skeletal muscle, supplying myonuclei for homoeostasis, hypertrophy and repair. In this study, we have examined the role of bone morphogenetic protein (BMP) signalling in regulating satellite cell function. Activated satellite cells expressed BMP receptor type 1A (BMPR-1A/Alk-3) and contained phosphorylated Smad proteins, indicating that BMP signalling is operating during proliferation. Indeed, exogenous BMP4 stimulated satellite cell division and inhibited myogenic differentiation. Conversely, interfering with the interactions between BMPs and their receptors by the addition of either the BMP antagonist Noggin or soluble BMPR-1A fragments, induced precocious differentiation. Similarly, blockade of BMP signalling by siRNA-mediated knockdown of BMPR-1A, disruption of the intracellular pathway by either Smad5 or Smad4 knockdown or inhibition of Smad1/5/8 phosphorylation with Dorsomorphin, also caused premature myogenic differentiation. BMP signalling acted to inhibit the upregulation of genes associated with differentiation, in part, through regulating Id1. As satellite cells differentiated, Noggin levels increased to antagonise BMP signalling, since Noggin knockdown enhanced proliferation and impeded myoblast fusion into large multinucleated myotubes. Finally, interference of normal BMP signalling after muscle damage in vivo perturbed the regenerative process, and resulted in smaller regenerated myofibres. In conclusion, BMP signalling operates during routine satellite cell function to help coordinate the balance between proliferation and differentiation, before Noggin is activated to antagonise BMPs and facilitate terminal differentiation.
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subjects 631/136/2060/2068
631/136/2091
631/80/86
Animals
Apoptosis
Biochemistry
Biomedical and Life Sciences
Biophysics
Bone Morphogenetic Protein 4 - genetics
Bone Morphogenetic Protein 4 - metabolism
Bone Morphogenetic Protein 4 - pharmacology
Bone Morphogenetic Protein Receptors, Type I - genetics
Bone Morphogenetic Protein Receptors, Type I - metabolism
Bone Morphogenetic Proteins - antagonists & inhibitors
Bone Morphogenetic Proteins - metabolism
Bone Morphogenetic Proteins - physiology
Carrier Proteins - genetics
Carrier Proteins - metabolism
Carrier Proteins - pharmacology
Cell Biology
Cell Cycle Analysis
Cell death
Cell Differentiation
Cell division
Cell Proliferation
Kinases
Life Sciences
Mice
Musculoskeletal system
Myogenesis
Original Paper
Phosphorylation
Proteins
Pyrazoles - pharmacology
Pyrimidines - pharmacology
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
Recombinant Proteins - pharmacology
Repair & maintenance
RNA Interference
RNA, Small Interfering - metabolism
Satellite Cells, Skeletal Muscle - cytology
Signal Transduction
Smad Proteins - genetics
Smad Proteins - metabolism
Stem Cells
title BMP signalling permits population expansion by preventing premature myogenic differentiation in muscle satellite cells
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