title: Matrix gla protein: An extracellular matrix protein regulates myostatin expression in the muscle developmental program.
abstract: OBJECTIVE
  Skeletal muscle development involves interactions between intracellular and extracellular factors that act in concert to regulate the myogenic process. Matrix gla protein (MGP), a well-known inhibitor of calcification in soft tissues, has been reported to be highly up-regulated during myogenesis. Our interest in the regulation of muscle satellite cells (MSCs) by extracellular matrix (ECM) led us to investigate the effects of MGP during the progression of myogenesis.
  
  
  METHODS
  Participation of MGP in the myogenic process was investigated in vitro using C2C12 cells, and knockdown of its gene was performed to determine its effects on the expression of myogenic regulatory factors (MRFs) and other ECM genes. In addition, interactions between MGP, Fibromodulin (FMOD), and Myostatin (MSTN) were investigated by conducting co-immunoprecipitation and in silico studies.
  
  
  RESULTS
  Matrix gla protein knockdown (MGPkd) shows pronounced effects during myogenesis as evidenced by the down regulation of myogenic marker (MYOG and MYOD), and ECM (COL1α1 and FMOD) genes. Down-regulation of MSTN expression in MGPkdcells suggests its role in coordinating the regulation of MSTN expression. Having strong affinity for ACVRIIB receptor, in silico data confirms MGP interference in the interaction of MSTN with ACVRIIB. These findings show MGP inhibits MSTN functionally by disrupting its binding to receptor.
  
  
  CONCLUSIONS
  The present study provides insights of an ECM protein that participates in the regulation of the myogenic program by inhibiting the activity of the myogenic negative regulator MSTN, which suggests that MGP might be used for designing novel inhibitors that can promote muscle regeneration or treat muscle atrophy.
authors.affiliation: Department of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, Republic of Korea.
authors.forename: Sarafraz
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: Department of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, Republic of Korea.
authors.forename: Arif Tasleem
authors.initials: AT
authors.lastname: Jan
authors.affiliation: Department of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, Republic of Korea.
authors.forename: Mohammad Hassan
authors.initials: MH
authors.lastname: Baig
authors.affiliation: Department of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, Republic of Korea.
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Department of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, Republic of Korea. Electronic address: inhochoi@ynu.ac.kr.
authors.forename: Inho
authors.initials: I
authors.lastname: Choi
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism*; D055435:Myostatin / Q000378:metabolism*; D000097568:Matrix Gla Protein
chemical_list: D020746:Calcium Channels, L-Type; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D055435:Myostatin; D000097568:Matrix Gla Protein
keywords: Extracellular matrix; Matrix gla protein; Muscle satellite cells; Myoblast differentiation; Myostatin