title: BMP signaling balances proliferation and differentiation of muscle satellite cell descendants.
abstract: BACKGROUND
  The capacity of muscle to grow or to regenerate after damage is provided by adult stem cells, so called satellite cells, which are located under the basement lamina of each myofiber. Upon activation satellite cells enter the cell cycle, proliferate and differentiate into myoblasts, which fuse to injured myofibers or form new fibers. These processes are tightly controlled by many growth factors.
  
  
  RESULTS
  Here we investigate the role of bone morphogenetic proteins (BMPs) during satellite cell differentiation. Unlike the myogenic C2C12 cell line, primary satellite cells do not differentiate into osteoblasts upon BMP signaling. Instead BMP signaling inhibits myogenic differentiation of primary satellite cells ex vivo. In contrast, inhibition of BMP signaling results in cell cycle exit, followed by enhanced myoblast differentiation and myotube formation. Using an in vivo trauma model we demonstrate that satellite cells respond to BMP signals during the regeneration process. Interestingly, we found the BMP inhibitor Chordin upregulated in primary satellite cell cultures and in regenerating muscles. In both systems Chordin expression follows that of Myogenin, a marker for cells committed to differentiation.
  
  
  CONCLUSIONS
  Our data indicate that BMP signaling plays a critical role in balancing proliferation and differentiation of activated satellite cells and their descendants. Initially, BMP signals maintain satellite cells descendants in a proliferating state thereby expanding cell numbers. After cells are committed to differentiate they upregulate the expression of the BMP inhibitor Chordin thereby supporting terminal differentiation and myotube formation in a negative feedback mechanism.
authors.affiliation: Center for Medical Biotechnology, Faculty of Biology, Department of Developmental Biology, University of Duisburg-Essen, D-45117 Essen, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Friedrichs
authors.forename: Florian
authors.initials: F
authors.lastname: Wirsdöerfer
authors.forename: Stefanie B
authors.initials: SB
authors.lastname: Flohé
authors.forename: Sabine
authors.initials: S
authors.lastname: Schneider
authors.forename: Manuela
authors.initials: M
authors.lastname: Wuelling
authors.forename: Andrea
authors.initials: A
authors.lastname: Vortkamp
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D049109:Cell Proliferation; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D012038:Regeneration; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D019485:Bone Morphogenetic Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; D051785:Smad Proteins; C054234:chordin