Critical Reviews in Oral Biology & Medicine, Vol 12, 373-398, Copyright © 2001 by International & American Associations for Dental Research
Proteolytic events of wound-healing--coordinated interactions among matrix metalloproteinases (MMPs), integrins, and extracellular matrix molecules
B. Steffensen, L. Hakkinen and H. Larjava
Department of Periodontics, University of Texas Health Science Center at San Antonio, 78229-3900, USA. steffensenb@uthscsa.edu
During wound-healing, cells are required to migrate rapidly into the wound
site via a proteolytically generated pathway in the provisional matrix, to
produce new extracellular matrix, and, subsequently, to remodel the newly
formed tissue matrix during the maturation phase. Two classes of molecules
cooperate closely to achieve this goal, namely, the matrix adhesion and
signaling receptors, the integrins, and matrix-degrading and -processing
enzymes, the matrix metalloproteinases (MMPs). There is now substantial
experimental evidence that blocking key molecules of either group will
prevent or seriously delay wound-healing. It has been known for some time
now that cell adhesion by means of the integrins regulates the expression
of MMPs. In addition, certain MMPs can bind to integrins or other receptors
on the cell surface involved in enzyme activation, thereby providing a
mechanism for localized matrix degradation. By proteolytically modifying
the existing matrix molecules, the MMPs can then induce changes in cell
behavior and function from a state of rest to migration. During wound
repair, the expression of integrins and MMPs is simultaneously
up-regulated. This review will focus on those aspects of the extensive
knowledge of fibroblast and keratinocyte MMPs and integrins in biological
processes that relate to wound-healing.
