Matrix metalloproteinases and tissue inhibitors of metalloproteinases in joint fluid of the patients with loose artificial hip joints.

Matrix metalloproteinases and tissue inhibitors of metalloproteinases in joint fluid of the patients with loose artificial hip joints.
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人工髋关节松动患者关节液中基质金属蛋白酶和金属蛋白酶组织抑制剂的研究

DOI:
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发表时间:
1999
期刊:
Journal of Biomedical Materials Research
影响因子:
--
通讯作者:
Y. Konttinen
Y. Konttinen
中科院分区:
--
文献类型:
--
作者:
I. Takei;M. Takagi;S. Santavirta;H. Ida;M. Hamasaki;M. Ishii;S. Fukushima;T. Ogino;Y. Konttinen

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在接受全髋关节置换术(THA)的患者中形成的假关节腔后来被重塑为滑膜样组织,从而产生假滑液。这种假滑膜也是基质金属蛋白酶(MMPs)的重要来源。由于人们普遍推测滑液MMPs可能导致类风湿性关节炎(RA)和骨关节炎(OA)的局部组织降解,我们假设在假滑液中发现了局部产生的MMPs,通过假滑液MMPs可以进入植入物-宿主界面,如果它们保留其蛋白水解潜力,则可能导致无菌性松动。采用酶联免疫吸附试验(ELISA)、免疫印迹法和酶谱法检测无菌性松动关节滑液中MMPs和金属蛋白酶组织抑制剂(TIMPs)的含量,并与RA和OA进行比较。假性滑膜THA液的特征在于使用低水平的MMP-1,但中等水平的MMP-13和MT1-MMP(MMP-14)。由于缺乏适当的分析,MMP-13和MT1-MMP没有进行类似的评估,但免疫印迹表明它们是56 kD的中间蛋白水解加工形式。MMP-9水平介于RA和OA之间。MMP-2表达有显著性差异,但各组间无显著性差异。THA组的特征还在于使用相对高水平的TIMP-1和TIMP-2。因此,发现MMP-9和MMP-2分别以92 kD和72 kD酶原形式存在,在所有研究组中均保留完全活性。这些数据表明,proMMP-2-TIMP-2和proMMP-9-TIMP-1复合物是由于THA无菌性松动中TIMP超过MMP而在假滑液中形成的。TIMP-复合的MMP对MMP-介导的蛋白水解活化具有抗性,这可以解释它们的潜伏期和酶原酶原的形式。因此,稳定proMMP-TIMP复合物的形成使得proMMP能够远离其原始产生位点运输。由于关节内压力的运动相关周期性变化,由TIMP稳定的液相MMPs可能被吸收到植入物表面和界面组织,并有助于原位分离植入物/骨水泥-骨界面。因此,它们可能导致局部蛋白水解/组织破坏事件和无菌性松动。
The pseudojoint cavity formed in patients undergoing total hip arthroplasty (THA) is later remodeled to synovial membrane-like tissue, which produces pseudosynovial fluid. This pseudosynovium also is an important source of matrix metalloproteinases (MMPs). As it is widely speculated that synovial fluid MMPs may contribute to local tissue degradation in rheumatoid arthritis (RA) and osteoarthritis (OA), we hypothesize that locally produced MMPs are found in the pseudosynovial fluid, via which they have access to the implant-host interface, and that if they retain their proteolytic potential, they might contribute to aseptic loosening. Enzyme-linked immunosorbent assay (ELISA), immunoblotting, and zymography were used to analyze MMPs and tissue inhibitors of metalloproteinases (TIMPs) in synovial fluid in aseptic loosening, which was compared to RA and OA. Pseudosynovial THA fluid was characterized using low levels of MMP-1 but moderate levels of MMP-13 and MT1-MMP (MMP-14). Due to the lack of an appropriate assay, MMP-13 and MT1-MMP were not similarly assessed, but the immunoblotting indicated that they were in the 56 kD intermediate proteolytically processed forms. The MMP-9 level was intermediate between RA and OA. MMP-2 was on a significant level, but there were no differences among study groups. The THA group also was characterized using relatively high levels of TIMP-1 and TIMP-2. Accordingly, MMP-9 and MMP-2 were found to occur in the 92 kD and 72 kD proenzyme form, respectively, with full activity retained in all study groups. The data suggest that proMMP-2-TIMP-2 and proMMP-9-TIMP-1 complexes are formed in the pseudosynovial fluid due to the excess of TIMPs over MMPs in aseptic loosening of THA. TIMP-complexed MMPs are resistant to MMP-mediated proteolytic activation, which may explain their latency and proenzyme zymogen form. Thus, formation of stabilizing proMMP-TIMP complexes enable transportation of proMMPs far from their original site of production. Due to motion-associated cyclic changes of the intra-articular pressure, fluid-phase MMPs stabilized by TIMPs might be absorbed to implant surfaces and interface tissues and help to dissect the implant/cement-to-bone interface in situ. Consequently, they may contribute to local proteolytic/tissue destructive events and aseptic loosening.
松散的全髋关节假体周围的细胞外基质金属蛋白酶。
DOI: 10.3109/17453679408995454
发表时间: 1994
期刊: Acta orthopaedica Scandinavica
影响因子: --
作者:
Takagi,M;Konttinen,YT;Santavirta,S;Sorsa,T;Eisen,AZ;Nordsletten,L;Suda,A
通讯作者: Suda,A
DOI: --
发表时间: 1993-07
期刊: The Journal of biological chemistry
影响因子: --
作者:
A. Strongin;B. Marmer;G. A. Grant;G. Goldberg
通讯作者: A. Strongin;B. Marmer;G. A. Grant;G. Goldberg
DOI: --
发表时间: 1986-05
期刊: The Journal of biological chemistry
影响因子: --
作者:
G. Goldberg;S. Wilhelm;A. Kronberger;E. Bauer;G. A. Grant;A. Eisen
通讯作者: G. Goldberg;S. Wilhelm;A. Kronberger;E. Bauer;G. A. Grant;A. Eisen