Increased inflammation delays wound healing in mice deficient in collagenase-2 (MMP-8)

FASEB J. 2007 Aug;21(10):2580-91. doi: 10.1096/fj.06-7860com. Epub 2007 Mar 28.


Matrix metalloproteinases (MMPs) have been implicated in numerous tissue-remodeling processes. The finding that mice deficient in collagenase-2 (MMP-8) are more susceptible to develop skin cancer, prompted us to investigate the role of this protease in cutaneous wound healing. We have observed a significant delay in wound closure in MMP8-/- mice and an altered inflammatory response in their wounds, with a delay of neutrophil infiltration during the first days and a persistent inflammation at later time points. These changes were accompanied by alterations in the TGF-beta1 signaling pathway and by an apoptosis defect in MMP8-/- mice. The delay in wound healing observed in MMP8-/- mice was rescued by bone marrow transplantation from wild-type mice. Analysis of other MMPs showed that MMP8-/- mice had a significant increase in the expression of MMP-9, suggesting that both proteases might act coordinately in this process. This possibility was further supported by the novel finding that MMP-8 and MMP-9 form specific complexes in vivo. Taken together, these data indicate that MMP-8 participates in wound repair by contributing to the resolution of inflammation and open the possibility to develop new strategies for treating wound healing defects.

Publication types

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

MeSH terms

  • Animals
  • Bone Marrow Transplantation / physiology
  • Genetic Predisposition to Disease
  • In Situ Hybridization
  • Inflammation / physiopathology*
  • Matrix Metalloproteinase 8 / deficiency*
  • Matrix Metalloproteinase 8 / genetics
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Knockout
  • Skin Neoplasms / genetics
  • Wound Healing / physiology*


  • Matrix Metalloproteinase 8
  • Matrix Metalloproteinase 9