Increased expression of the β₁, α₅ and α_v integrin adhesion receptor subunits occurs coincident with remodeling of stress‐deprived rabbit anterior cruciate and medial collateral ligaments

Abstract

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Up‐regulation of oligodendrocyte precursor cell αV integrin and its extracellular ligands during central nervous system remyelination

“…The mechanisms uncovered by the cell culture studies may therefore be those activated during repair rather than those required for normal development, and further studies using the conditional knockout animals are required to test this hypothesis. Significant increases in aV integrin expression have also been observed during regeneration in a number of non-neural tissues (AbiEzzi et al, 1995;Pilewski et al, 1997;Tsonis et al, 1997;Noszczyk et al, 2002). Taken together with our present data, this suggests that aV integrins may have a specific role in regenerative processes.…”

Integrin signaling in skeletal development and function

“…These results correlate with previous findings on the augmented fibronectin deposition and angiogenesis in the early phases after tendon rupture, suggesting an important role of fibronectin–integrin adhesion events during tendon repair (Amiel et al, ; Gelberman et al, ). It seems that the fibronectin‐binding α5β1 receptor might be also involved during tissue remodeling after ligament immobilization, since it was reported that in stress‐deprived ligaments the expression of α5β1 is markedly increased (AbiEzzi et al, ). Another study investigated the effect of fatigue on the expression of integrin subunits α11 and β1 in rat patellar tendons and found a differential response, as a downregulation of α11 and an upregulation of β1 was observed.…”

The influence of the mechanical environment on remodelling of the patellar tendon

“…These include an increase in the number of fibroblasts, 12,36 of the number of small collagen fibrils, 36,37 the expression of manganese superoxide dismutase, 38 and the expression of cytokines such as IL-1β, TNF-α and TGF-β. 39 Abiezzi et al 40 described an increase in integrin adhesion subreceptor units in conjunction with the remodelling of stress-deprived rabbit ligaments. Mechanical strain has recently been shown to stimulate the conformational activation of integrins directly.…”