INCREASED EXPRESSION OF THE BETA(1), ALPHA(5), AND ALPHA(V) INTEGRIN ADHESION RECEPTOR SUBUNITS OCCURS COINCIDENT WITH REMODELING OF STRESS-DEPRIVED RABBIT ANTERIOR CRUCIATE AND MEDIAL COLLATERAL LIGAMENTS

The biomechanical, biochemical, and morphological properties of the anterior cruciate and medial collateral Ligaments are dramatically altered in response to deprivation of normal physical forces and joint motion. Integrin adhesion receptors are known to play important roles in the tissue remodeling that occurs in the course of normal wound repair. We propose that integrins play a similar role in the remodeling of the extracellular matrix in stress-deprived periarticular ligaments. This study tests the hypothesis that altered expression of integrins on ligament fibroblasts accompanies this remodeling. The left knees of 15 New Zealand White rabbits were surgically immobilized in acute flexion and the right knees served as controls (no operation). The anterior cruciate and medial collateral ligaments were harvested at 1, 3, 5, 9, or 12 weeks after immobilization. Sections from the ligaments were immunostained with monoclonal antibodies specific for the integrin subunits beta(1), alpha(5), alpha 6, and alpha(v), as well as with a negative control antibody. Fibroblasts within both the stress-deprived anterior cruciate and medial collateral ligaments demonstrated markedly increased staining for the beta(1), alpha(5), and alpha(v) subunits, as compared with the controls. The increased staining was greatest at 9 weeks in the anterior cruciate ligament and at 12 weeks in the medial collateral ligament. Western blot study of ligament proteins extracted with sodium dodecyl sulfate demonstrated an increased amount of beta(1) subunit protein in both ligaments from knees that were stress deprived for 9 and 12 weeks, as compared with the control ligaments. These studies establish that stress deprivation in this animal model is accompanied by increased expression of integrin cell-surface receptors containing the beta(1), alpha(5), and alpha(v) subunits on anterior cruciate and medial collateral ligament fibroblasts, with a time course similar to that previously reported for indices of extracellular matrix remodeling induced by stress deprivation. This outcome suggests an important role for these integrins in the remodeling of stress-deprived ligaments.