| Co-Investigator(Kenkyū-buntansha) |
SATO Keiji Aichi Medical University, Professor, 教授 (20178726)
ISHIGURO Naoki Nagoya University school of medicine, Lecturer, 医学部, 講師 (20212871)
HASEGAWA Yukiharu Nagoya University school of medicine, Lecturer, 医学部, 講師 (50208500)
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| Research Abstract |
Matrix metalloproteinases (MMPS) and tissue inhibitors of metalloproteinase (TIMPs) play an important role in tissue destruction and remodeling. We focused the synvial fluid and interface tissue of loosening THA.We revealed. these points.
Extremely high concentrations of MMP-3 in synovial fluid (SF) of the patients with RA may contribute to its elevation in serum. It would seem that regulation of TIMP production depends upon the dis-ease state and not the concentration of MMP.Discrepancies between concentrations of TIMP and MMP in SF may be responsible for cartilage destruction in RA.
The samples of cement inter-face tissues from patients who had failed cemented total hip arthroplasty (THA) were obtained for revision of THA and analyzed on mRNA expression of MMPs and TIMPs. We used the revers transcrip-tional polymerase chain reaction (RT-PCR). mRNA of MMP--1, -2, -3, -9, and TIMP-1 and -2 was detected in the interface tissue. MMP-10 mRNA was not detected, yet MMP-1 and MMP-3 mRNA were c
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ommonly observed.TIMT-2 mRNA was also strongly expressed compared to TIMP-1. It was thus demonstrated that MMPs and TIMPs were produced locally in the cement bone interface tissue of THA loosening.
Also we revealed that polyethylene debris sur-rounded by macrophages and phagocytosis of debris by macrophages was frequently observed in the interface tissue. Macrophage activation and the production of inflammatory cytokines such as IL-1 and TNFa might induce the development of interface tissue. Expression of chemokine mRNAs was also commonly seen, suggesting that this led to recruitment of macrophages into the bone cement interface tissue. Debris released from implants appears to cause activation of macrophages and the production of inflammatory cytokines and chemokines that induce cellular recruitment into interface tissue. We suggested the mechanism might form a vicious cycle that aggravates THA loosening.
We tryed to develop new treatment of disc herniation using chondroitinase ABC.Experimental chemonucleolysis with chondroitinase ABC as compared with chymopapain, was investigated in monkeys. The effects of these two enzyms were analyzed morphologically and biochemically. The results confirm that selective degradation is achived with chondroitinase ABC in monkeys and that chondroitinase ABC is less toxic to discs than chymopapain is.
Also, we investigated the posttranscriptional regulation of tissue matrix. So, the kinetics of type I procollagen synthesis in a human osteosarcoma cell line, MG 63, were investigated after treatment with 1,25-dihydroxyvitamin D.The results therefore suggest an increase in both the synthesis and secretion of type I collagen. Moreover, gelatinase B-resistant procollagen molecules, indicative of intracellular procollagen molecules in the stable triple helical form, were detected only in the 1,25-(OH)2 D,-treated cells. The present evidence points to posttranslational control of procollagen synthesis. Less
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