Regulation of TIMP-2, MT1-MMP, and MMP-2 expression during C2C12 differentiation

Muscle Nerve. 2005 Oct;32(4):492-9. doi: 10.1002/mus.20383.


Matrix metalloproteinases (MMPs) are zinc-dependent proteases capable of degrading extracellular matrix components. The activity of these proteases is tightly regulated through the actions of the tissue inhibitors of metalloproteinases (TIMPs). Although the regulation of MMPs and TIMPs during physiological and pathological remodeling has been investigated in a number of systems, almost nothing is known about their role in skeletal muscle differentiation. To investigate the role of MMP-mediated proteolysis during myogenesis, the regulation of TIMP-2, MT1-MMP, and MMP-2 expression was investigated during differentiation of the mouse myoblastic C2C12 cell line. We show that this trio is upregulated coincident with myogenesis. The more diffuse spatial distribution of TIMP-2 relative to MT1-MMP and MMP-2 suggests that TIMP-2 may exert MMP-independent functions during myogenesis. Elucidating the regulation of these molecules during muscle differentiation in vitro may lead to a better understanding of their role in pathological processes in muscle tissue in vivo.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Differentiation / physiology*
  • Cell Movement
  • Cells, Cultured
  • DNA, Complementary / genetics
  • Gene Expression Regulation, Developmental*
  • Immunohistochemistry
  • In Vitro Techniques
  • Matrix Metalloproteinase 14
  • Matrix Metalloproteinase 2 / biosynthesis*
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases / biosynthesis*
  • Metalloendopeptidases / genetics
  • Mice
  • Muscle Development / physiology*
  • Myoblasts, Skeletal* / cytology
  • Myoblasts, Skeletal* / enzymology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Inhibitor of Metalloproteinase-2 / biosynthesis*
  • Tissue Inhibitor of Metalloproteinase-2 / genetics


  • DNA, Complementary
  • Mmp14 protein, mouse
  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 14