MGF enhances tenocyte invasion through MMP-2 activity via the FAK-ERK1/2 pathway

Wound Repair Regen. 2015 May-Jun;23(3):394-402. doi: 10.1111/wrr.12293. Epub 2015 Jun 19.

Abstract

Tendon regeneration and healing requires tenocytes to move to the repair site followed by proliferation and synthesis of the extracellular matrix. A novel synthetic growth factor, mechano-growth factor (MGF), has been discovered to have positive roles in tissue repair through the improvement of cell proliferation and migration and the protection of cells against injury-induced apoptosis. However, it remains unclear whether MGF has the potential to accelerate tendon repair. In this study, using a transwell system, we found that MGF-C25E (a synthetic mechano-growth factor E peptide) significantly promotes tenocyte invasion, which was accompanied by the increased phosphorylation of focal adhesion kinase (FAK) and extracellular signal regulated kinase1/2 (ERK1/2) as well as the increased activity of matrix metalloproteinases-2 (MMP-2). The MMP-2 inhibitor OA-Hy blocked MGF-C25E-promoted tenocyte invasion. Inhibitors of FAK or ERK1/2 blocked MGF-C25E-promoted tenocyte invasion and MMP-2 activity as well. These results indicate that MGF-C25E promotes tenocyte invasion by increasing MMP-2 activity via the FAK-ERK1/2 signaling pathway. Taken together, our findings provide the first evidence that MGF-C25E enhances tenocyte invasion and indicate that it may serve as a potential repair material for promoting the healing and regeneration of injured tendons.

Keywords: Extracellular signal regulated kinase1/2; Focal adhesion kinase; Invasion; Matrix metalloproteinases-2; Mechano-growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Achilles Tendon / cytology
  • Achilles Tendon / injuries
  • Achilles Tendon / pathology*
  • Animals
  • Cell Proliferation
  • Disease Models, Animal
  • Focal Adhesion Kinase 1 / metabolism*
  • Focal Adhesion Kinase 1 / physiology
  • Insulin-Like Growth Factor I / metabolism*
  • MAP Kinase Signaling System / physiology*
  • Male
  • Matrix Metalloproteinase 2 / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Regeneration
  • Wound Healing*

Substances

  • mechano-growth factor, rat
  • Insulin-Like Growth Factor I
  • Focal Adhesion Kinase 1
  • Matrix Metalloproteinase 2