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重要作用。我们聚焦于关节液和松动THA的界面组织。RA患者滑液中MMP-3浓度过高可能与血清中MMP-3浓度升高有关。提示TIMP的产生与疾病状态有关，而与MMP的浓度无关，SF中TIMP和MMP的浓度差异可能是RA软骨破坏的原因之一。采用逆转录聚合酶链反应（RT-PCR）。MMP-1、MMP-2、MMP-3、MMP-9和TIMP-1、TIMP-2的mRNA在界面组织中表达。MMP-1、MMP-3 mRNA表达与MMP-10 mRNA表达呈负相关，而MMP-10 mRNA表达与MMP-1 mRNA表达呈负相关。 ...更多信息 TIMT-2 mRNA的表达也较TIMP-1强。结果表明，在THA松动的骨水泥-骨界面组织中，MMPs和TIMPs在骨水泥-骨界面组织中局部产生，界面组织中聚乙烯碎片被巨噬细胞包围，巨噬细胞对聚乙烯碎片的吞噬作用也较强。巨噬细胞活化和炎性细胞因子如IL-1和TNF α的产生可能诱导界面组织的发育。还常见趋化因子mRNA的表达，表明这导致巨噬细胞募集到骨水泥界面组织中。从植入物释放的碎片似乎会引起巨噬细胞的活化以及诱导细胞募集到界面组织中的炎性细胞因子和趋化因子的产生。我们尝试用软骨素酶ABC治疗椎间盘突出症，并与木瓜凝乳蛋白酶进行了比较。从形态学和生化学角度分析了这两种酶的作用。结果证实，选择性降解实现与软骨素酶ABC在猴子和软骨素酶ABC是较低的毒性光盘比chymopapain是。此外，我们研究了组织基质的转录后调控。因此，在人骨肉瘤细胞系MG 63中，I型前胶原合成的动力学在用1，25-二羟基维生素D处理后进行了研究。因此，结果表明I型胶原的合成和分泌增加。此外，明胶酶B-抗性前胶原分子，在稳定的三螺旋形式的细胞内前胶原分子的指示，仅在1，25-（OH）2-D，-处理的细胞中检测到。目前的证据表明，前胶原合成的翻译后控制。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