Biomedical subjects

P J Schreck

Publications and source records attributed to P J Schreck.

4 recordsLinked to original sources

PubMed1995

Integrin display increases in the wounded rabbit medial collateral ligament but not the wounded anterior cruciate ligament.

The differential capacities of the anterior cruciate and medial collateral ligaments to heal may be related to differences in cellular function. This study tested the hypothesis that differential expression of integrins occurs in these ligaments after injury. The integrins are a family of cell surface receptors that mediate adhesion, migration, and other cellular functions critical to the healing of a wound. A similar complement and amount of the beta 1 subfamily of integrins are known to be present on the unperturbed anterior cruciate and medial collateral ligaments in humans and rabbits. A partial laceration was surgically created in these two ligaments in 12 anesthetized New Zealand White rabbits. Immunohistochemistry was performed on sections from the ligaments at 1, 3, 7, and 10 days after injury, using monoclonal antibodies directed against the integrin subunits beta 1, alpha 5, alpha 6, and alpha v. Between 3 and 7 days, the wounded medial collateral ligament demonstrated a striking increase in staining for the beta 1, alpha 5, and alpha v subunits on the fibroblasts, within the repair site, and on capillary endothelium. Increased staining was most marked for the beta 1 subunit and less marked for the alpha 5 and alpha v subunits. The alpha 6 subunit stained exclusively vascular structures within the healing medial collateral ligament. In marked contrast, the anterior cruciate ligament, which does not mount an effective repair response, demonstrated no comparable alteration of integrin expression from baseline levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Integrin expression by human articular chondrocytes.

OBJECTIVE: To perform a comprehensive analysis of the integrin forms expressed by normal human articular chondrocytes. METHODS: Cartilage sections and collagenase-released chondrocytes were probed with a comprehensive panel of integrin isoform-specific monoclonal antibodies (MAb), using in situ immunohistochemistry techniques, indirect immunofluorescence and flow cytometry, and immunoprecipitation/sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). RESULTS: Chondrocytes in cartilage sections reacted with MAb specific for the alpha 5, alpha v, and beta 1 integrin subunits and the alpha v beta 3 and alpha v beta 5 heterodimers. They also reacted with a polyclonal antibody specific for the intracytoplasmic portion of the alpha 1 subunit. MAb specific for the alpha v subunit reacted more strongly with chondrocytes near the articular surface than with those in deeper layers of cartilage, and the alpha v beta 3-specific MAb reacted exclusively with chondrocytes within the most superficial 30 microns of cartilage. Flow cytometric analysis and SDS-PAGE analysis of immunoprecipitates prepared from extracts of cell-surface radioiodinated chondrocytes confirmed the above observations, and additionally revealed the presence of the alpha 3 beta 1 integrin. CONCLUSION: Normal human articular chondrocytes prominently display substantial quantities of the alpha 1 beta 1, alpha 5 beta 1, and alpha v beta 5 integrin heterodimers, as well as lesser quantities of the alpha 3 beta 1 and alpha v beta 3 heterodimers. The alpha v subunit-containing integrins are detected more readily on the more superficial chondrocytes than on chondrocytes deep within cartilage. These observations provide the basis for analysis of the role of chondrocyte integrins in cartilage homeostasis and in the pathogenesis of joint diseases.

Adult↗

PubMed1992

Immunohistochemical localization of beta 1-integrins in anterior cruciate and medial collateral ligaments of human and rabbit.

The integrins are a family of adhesion-mediating cell surface receptors that play critical roles in cell-extracellular matrix interactions and have been shown to be important in the healing response in several tissues. We have studied integrin expression in normal human and rabbit anterior cruciate (ACL) and medial collateral (MCL) ligaments of the knee as a preamble to studies of beta 1-integrin expression in healing ligaments. Histologic sections of human and rabbit ACL and MCL were probed for integrin expression utilizing integrin-specific monoclonal antibodies (mAbs) followed by immunoperoxidase detection. Staining of human specimens with mAbs revealed the presence of beta 1-, alpha 1-, and alpha 5-integrin chains on the tissue fibroblasts of both ACL and MCL, while staining of rabbit specimens with rabbit integrin-reactive monoclonals revealed the presence of beta 1- and alpha 5-integrin on these ligaments. Equivalent amounts of the integrins studied were present on normal ACL and MCL. We conclude that the rabbit is an appropriate model for analyzing the expression and functional role of integrins in ligament wound healing.

Animals↗