Extracellular matrix in bone and cartilage destruction.

基质金属蛋白酶（MMPS）和金属蛋白酶组织抑制剂（TIMPs）在组织破坏和重塑中起着重要作用。我们聚焦于松解THA的滑膜液和界面组织。我们发现。这些点。类风湿性关节炎患者滑液（SF）中MMP-3的极高浓度可能导致血清中MMP-3的升高。似乎TIMP产生的调节取决于疾病状态，而不是MMP的浓度。SF中TIMP和MMP浓度的差异可能是RA中软骨破坏的原因。对骨水泥全髋关节置换术（THA）失败患者的骨水泥界面组织样本进行THA翻修，并分析MMPs和TIMPs mRNA表达。我们使用逆转录聚合酶链反应（RT-PCR）。在界面组织中检测到MMP- 1、-2、-3、-9和TIMP-1和-2的mRNA。MMP-10 mRNA未检出，MMP-1和MMP-3 mRNA检出较多。与TIMP-1相比，TIMT-2 mRNA也强烈表达。这表明MMPs和TIMPs是在THA松动的水泥骨界面组织中局部产生的。我们还发现，在界面组织中经常观察到巨噬细胞包围聚乙烯碎片和巨噬细胞吞噬碎片的现象。巨噬细胞的活化和IL-1、TNFa等炎性细胞因子的产生可诱导界面组织的发育。趋化因子mrna的表达也很常见，这表明这导致巨噬细胞募集到骨水泥界面组织。植入物释放的碎片似乎会引起巨噬细胞的激活和炎症细胞因子和趋化因子的产生，从而诱导细胞募集到界面组织。我们认为这种机制可能形成恶性循环，加剧THA松动。我们尝试用软骨素酶ABC开发新的治疗椎间盘突出症的方法。研究了软骨素酶ABC与乳清蛋白酶在猴子体内的化学解核作用。对这两种酶的作用进行了形态学和生化分析。结果证实，猴子体内的软骨素酶ABC可选择性降解，而且软骨素酶ABC对椎间盘的毒性比乳脂蛋白酶小。此外，我们还研究了组织基质的转录后调控。因此，我们研究了1,25-二羟基维生素d在人骨肉瘤细胞系MG 63中I型前胶原合成的动力学，结果表明I型胶原的合成和分泌都有所增加。此外，仅在1,25-(OH) 2d处理的细胞中检测到抗明胶酶b的前胶原分子，表明细胞内前胶原分子呈稳定的三螺旋形式。目前的证据指向翻译后对前胶原合成的控制。少

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 … More 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