Upregulation of enzymatic activity by interleukin-1 in osteoarthritis
Upregulation of enzymatic activity by interleukin-1 in osteoarthritis
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DOI：
10.1016/s0753-3322(97)87727-x
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发表时间：
1997-01-01
影响因子：
7.5
通讯作者：
Chevalier, X
中科院分区：
文献类型：
--
作者：
Chevalier, X
骨关节炎是一种以关节软骨破坏为特征的缓慢进行性疾病。细胞外基质成分的降解主要由金属蛋白酶（MMPs）家族介导，其在中性pH下具有活性。白细胞介素-1（IL-1）是一种小肽，以自分泌和旁分泌方式具有活性。在体外IL-1增加MMPs的产生并抑制II型胶原和蛋白多糖的合成。其在骨关节炎中的作用基于几个发现：IL-1在骨关节炎关节的滑液和软骨基质中可检测到;在体内，其有害作用可通过关节内注射重组IL-1再现;在骨关节炎关节的软骨基质中观察到的生物化学变化类似于IL-1在体外诱导的生物化学变化;最后，IL-1拮抗剂能够在体内预防或至少减少几种实验性关节炎模型中软骨基质组分的降解。白细胞介素-1似乎是介导软骨基质破坏的主要因素。然而，它在人类骨关节炎中的作用，尽管可能性很高，但仍有待确定。
Osteoarthritis is a slow progressive disease characterized by destruction of the articular cartilage. The degradation of extracellular matrix components is mainly mediated by a family of enzymes, the metalloproteinases (MMPs), which ate active at neutral pH. Interleukin-1 (IL-1) is a small peptide, active in autocrine and paracrine fashions. In vitro IL-1 increases the production of MMPs and inhibits the synthesis of collagen type II and proteoglycans. Its role in osteoarthritis is based on several findings: IL-1 is detectable in the synovial fluid and in the cartilage matrix of osteoarthritic joints; in vivo its deleterious actions can be reproduced by intra-articular injection of recombinant IL-1; biochemical changes observed in the cartilage matrix from osteoarthritic joints resemble these induced in vitro by IL-1; finally, antagonists of IL-1 are capable in vivo of preventing or at least diminishing the degradation of cartilage matrix components in several models of experimental arthritis. Interleukin-1 appears to be a main factor mediating cartilage matrix destruction. However, its role in human osteoarthritis, although highly probable, remains to be determined.