Regeneration of soft tissues is promoted by MMP1 treatment after digit amputation in mice

PLoS One. 2013;8(3):e59105. doi: 10.1371/journal.pone.0059105. Epub 2013 Mar 18.

Abstract

The ratio of matrix metalloproteinases (MMPs) to the tissue inhibitors of metalloproteinases (TIMPs) in wounded tissues strictly control the protease activity of MMPs, and therefore regulate the progress of wound closure, tissue regeneration and scar formation. Some amphibians (i.e. axolotl/newt) demonstrate complete regeneration of missing or wounded digits and even limbs; MMPs play a critical role during amphibian regeneration. Conversely, mammalian wound healing re-establishes tissue integrity, but at the expense of scar tissue formation. The differences between amphibian regeneration and mammalian wound healing can be attributed to the greater ratio of MMPs to TIMPs in amphibian tissue. Previous studies have demonstrated the ability of MMP1 to effectively promote skeletal muscle regeneration by favoring extracellular matrix (ECM) remodeling to enhance cell proliferation and migration. In this study, MMP1 was administered to the digits amputated at the mid-second phalanx of adult mice to observe its effect on digit regeneration. Results indicated that the regeneration of soft tissue and the rate of wound closure were significantly improved by MMP1 administration, but the elongation of the skeletal tissue was insignificantly affected. During digit regeneration, more mutipotent progenitor cells, capillary vasculature and neuromuscular-related tissues were observed in MMP1 treated tissues; moreover, there was less fibrotic tissue formed in treated digits. In summary, MMP1 was found to be effective in promoting wound healing in amputated digits of adult mice.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amputation, Traumatic / drug therapy
  • Amputation, Traumatic / pathology*
  • Animals
  • Antigens, Ly / metabolism
  • Cicatrix / prevention & control
  • Extremities / pathology*
  • Male
  • Matrix Metalloproteinase 1 / administration & dosage
  • Matrix Metalloproteinase 1 / pharmacology*
  • Membrane Proteins / metabolism
  • Mice
  • Neovascularization, Physiologic / drug effects
  • Neural Cell Adhesion Molecules / metabolism
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Regeneration / drug effects*
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Time Factors
  • Wound Healing / drug effects*

Substances

  • Antigens, Ly
  • Ly6a protein, mouse
  • Membrane Proteins
  • Neural Cell Adhesion Molecules
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Matrix Metalloproteinase 1

Grants and funding

This study was partially support from NIH and DOD grants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.