Adeno-associated virus-mediated bone morphogenetic protein-7 gene transfer induces C2C12 cell differentiation into osteoblast lineage cells

Acta Pharmacol Sin. 2005 Aug;26(8):963-8. doi: 10.1111/j.1745-7254.2005.00159.x.

Abstract

Aim: To investigate the effects of bone morphogenetic protein-7 (BMP7)-expressing recombinant adeno-associated virus (AAV) vector on the differentiation of C2C12 cells.

Methods: AAV-BMP7 was packaged by infecting the stable cell clone BHK-21 (integrated with recombinant AAV vector plasmid pSNAV-BMP7) with recombinant herpes simplex virus type 1, which expresses AAV-2 Rep and Cap and possesses AAV packaging functions. Following infection with AAV-BMP7 at multiplicities of infection of 1 x 10(5) vector genomes per cell and subsequent culture, C2C12 cells were assessed qualitatively for BMP7 production, alkaline phosphatase activity, osteocalcin production and Cbfal and MyoD expression.

Results: C2C12 cells transduced with AAV-BMP7 could produce BMP7 protein until d 28. Alkaline phosphatase in the cultured C2C12 cell lysate was elevated. Secreted osteocalcin in the culture medium was detectable at d 12 and Cbfal mRNA expression level was upregulated, coinciding with downregulation of MyoD in a temporal manner.

Conclusion: The present in vitro study demonstrated that AAV-BMP7 could infect and efficiently convert C2C12 cells from myoblasts into osteoblast lineage cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins / biosynthesis
  • Bone Morphogenetic Proteins / genetics*
  • Bone Morphogenetic Proteins / physiology
  • Cell Differentiation*
  • Cell Line
  • Cell Lineage
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Dependovirus / genetics*
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression
  • Genetic Vectors / genetics
  • Humans
  • MyoD Protein / genetics
  • Myoblasts / cytology*
  • Myoblasts / metabolism
  • Osteoblasts / cytology*
  • Osteoblasts / metabolism
  • Osteocalcin / biosynthesis
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Time Factors
  • Transfection
  • Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta / physiology

Substances

  • BMP7 protein, human
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins
  • Core Binding Factor Alpha 1 Subunit
  • MyoD Protein
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Osteocalcin
  • Alkaline Phosphatase