Effect of cyclic tensile load on the regulation of the expression of matrix metalloproteases (MMPs -1, -3) and structural components in synovial cells.
Synovial cells are reported to colonize synthetic ligament scaffolds following anterior cruciate ligament (ACL) reconstruction but the process leading to ligamentization is poorly understood. The present study investigated the effect of cyclic tensile strain on the expression of genes involved in matrix remodelling in bovine synovial cells seeded onto an artificial ligament scaffold. Synovial cells were seeded and cultured on polyester scaffolds for 3 weeks and subsequently subjected to cyclic tensile strain of 4.5% for 1 hr at frequency of 1 Hz. Changes in the levels of expression of genes for major ligament components (type I and type III collagen) and also metalloproteinases (MMP-1 and MMP-3), and TIMP-1 were examined using RT-PCR. Additionally, metalloproteinase activity was measured using both zymography and collagenase assays. The gene expression of MMP-3 transcripts in the loaded group was almost 3-fold that observed in control group but no differences were observed in other transcripts. Consistent with these findings, MMP-3 activity increased by 85% under mechanical stimulus, and MMP-1 activity showed no changes. Over expression of MMP-3 under cyclic tensile load may mediate the proteolysis of certain substrates surrounding the ligament scaffold. This will play a critical role in facilitating cell migration, proliferation and tissue remodelling by breaking down the provisional tissue formed by the synovium, and by generating factors that induce angiogenesis and chemotactic cell migration.
Raïf
El Mostafa
el M
Division of Bioengineering, Academic Unit of Musculoskeletal and Rehabilitation Medicine, Leeds School of Medicine, Leeds, UK. medemro@leeds.ac.uk
D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D008022:Ligaments / Q000166:cytology / Q000502:physiology / Q000601:surgery; D020781:Matrix Metalloproteinase 1 / Q000235:genetics* / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics* / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D013314:Stress, Mechanical; D013583:Synovial Membrane / Q000166:cytology* / Q000201:enzymology* / Q000502:physiology; D013718:Tensile Strength; D023822:Tissue Engineering; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D054457:Tissue Scaffolds
D017931:DNA Primers; D019715:Tissue Inhibitor of Metalloproteinase-1; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1