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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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. |
doi_str_mv | 10.1038/cdd.2010.95 |
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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.</description><identifier>ISSN: 1350-9047</identifier><identifier>EISSN: 1476-5403</identifier><identifier>DOI: 10.1038/cdd.2010.95</identifier><identifier>PMID: 20689554</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>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</subject><ispartof>Cell death and differentiation, 2011-02, Vol.18 (2), p.222-234</ispartof><rights>Macmillan Publishers Limited 2011</rights><rights>Copyright Nature Publishing Group Feb 2011</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>Copyright © 2011 Macmillan Publishers Limited 2011 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-10d7dee07744ca08b1ff221730ff1f35b25af9d0429a1653e1b11c2f2ae2dce73</citedby><cites>FETCH-LOGICAL-c478t-10d7dee07744ca08b1ff221730ff1f35b25af9d0429a1653e1b11c2f2ae2dce73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044455/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044455/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,724,777,781,882,27905,27906,41469,42538,51300,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20689554$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-00563514$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Ono, Y</creatorcontrib><creatorcontrib>Calhabeu, F</creatorcontrib><creatorcontrib>Morgan, J E</creatorcontrib><creatorcontrib>Katagiri, T</creatorcontrib><creatorcontrib>Amthor, H</creatorcontrib><creatorcontrib>Zammit, P S</creatorcontrib><title>BMP signalling permits population expansion by preventing premature myogenic differentiation in muscle satellite cells</title><title>Cell death and differentiation</title><addtitle>Cell Death Differ</addtitle><addtitle>Cell Death Differ</addtitle><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.</description><subject>631/136/2060/2068</subject><subject>631/136/2091</subject><subject>631/80/86</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biophysics</subject><subject>Bone Morphogenetic Protein 4 - genetics</subject><subject>Bone Morphogenetic Protein 4 - metabolism</subject><subject>Bone Morphogenetic Protein 4 - pharmacology</subject><subject>Bone Morphogenetic Protein Receptors, Type I - genetics</subject><subject>Bone Morphogenetic Protein Receptors, Type I - metabolism</subject><subject>Bone Morphogenetic Proteins - antagonists & inhibitors</subject><subject>Bone Morphogenetic Proteins - metabolism</subject><subject>Bone Morphogenetic Proteins - 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Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell death and differentiation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ono, Y</au><au>Calhabeu, F</au><au>Morgan, J E</au><au>Katagiri, T</au><au>Amthor, H</au><au>Zammit, P S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>BMP signalling permits population expansion by preventing premature myogenic differentiation in muscle satellite cells</atitle><jtitle>Cell death and differentiation</jtitle><stitle>Cell Death Differ</stitle><addtitle>Cell Death Differ</addtitle><date>2011-02-01</date><risdate>2011</risdate><volume>18</volume><issue>2</issue><spage>222</spage><epage>234</epage><pages>222-234</pages><issn>1350-9047</issn><eissn>1476-5403</eissn><abstract>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. 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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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>20689554</pmid><doi>10.1038/cdd.2010.95</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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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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