| Co-Investigator(Kenkyū-buntansha) |
MIYAGI Noboru Hokkaido Univ., Medical Hospital, Inst.., 医学部附属病院, 助手 (90261297)
TOHYAMA Harukazu Hokkaido Univ., Grad. School of Medicine, Asso. Prof., 大学院・医学研究科, 助教授 (60301884)
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| Research Abstract |
1. This study biomechanically and molecular-biologically clarified the remodeling phenomenon of the patellar tendon (PT) and anterior cruciate ligament (ACL) tissues from the viewpoint of collagen synthesis and metabolism controlled by growth factors, using the in situ freeze-thaw treatment and several unique animal models which were originally developed by us. The results were shown as follows : (1) Intrinsic fibroblast necrosis did not significantly affect the mechanical properties of the PT, at least, for 6 weeks, but extrinsic fibroblast infiltration affected them. In addition, both stress deprivation and enhancement significantly deteriorated the mechanical properties of the in situ frozen ACL. (2) In the situ frozen PT, type-III procollagen mRNA was overexpressed in the extrinsic cells at 6 and 12 weeks, and type-III collagen was expressed around the extrinsic cells. (3) Application of IL-1beta and PDGF-BB enhanced expression of the collagenase mRNA in the extrinsic fibroblasts i
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n the frozen PT, while application of TGF-beta inhibited it. (4) Stress deprivation in the tendon tissue simultaneously induced not only overexpression of IL-1beta and TGF-beta-in fibroblasts but also reduction of the mechanical properties of the extracellular matrix. (5) A low-dose of TGF-β1 and EGF applied to the frozen-thawed ACL at 0 and 3 weeks inhibitd the material deterioration caused by freezing, but the same dose application at 6 weeks did not inhibit it. A high dose application did not inhibit it at each period. (6) Application of TGF-beta improves the material properties of healing tissue in the injured ACL, but application of the PDGF-BB does not have any effects.
2. In addition, this study established a new integrated analysis system to clarify adaptation and control mechanisms in remodeling of the tendon and ligament tissue, using the biomechanical and molecular-biological methods. As to clinical relevance, this study demonstrated a basic principle of therapeutic trials to inhibit the deterioration of the material properties of the grafted tendon and ligament tissues, which is a significant clinical problem at the present time. We believe that this principle will contribute development of gene therapy and tissue engineering-based treatment for the injured tendon and ligament tissues in the field of orthopaedic surgery and sports medicine. Less
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