Localization of matrix metalloproteinase 3 (stromelysin) in osteoarthritic cartilage and synovium.
Localization of matrix metalloproteinase 3 (stromelysin) in osteoarthritic cartilage and synovium.
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发表时间：
1992
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通讯作者：
Y. Okada;M. Shinmei;O. Tanaka;K. Naka;A. Kimura;Isao Nakanishi;M. Bayliss;K. Iwata;H. Nagase
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作者：
Y. Okada;M. Shinmei;O. Tanaka;K. Naka;A. Kimura;Isao Nakanishi;M. Bayliss;K. Iwata;H. Nagase
蛋白多糖的降解是骨关节炎软骨的最初变化。基质金属蛋白酶-3(MMP3；基质分解素)能降解软骨蛋白多糖和IX型胶原，免疫定位于骨关节炎和正常软骨。免疫组织化学研究显示，约90%的骨性关节炎软骨(67个样本中的60个)和31%的正常软骨(13个样本中的4个)浅表和移行区的软骨细胞中有基质金属蛋白酶-3的表达。MMP3染色与Mankin的组织学组织化学评分直接相关，与蛋白多糖耗竭直接相关，直至达到一定程度。只有当蛋白多糖耗竭和裂隙影响到深放射区、骨簇和骨赘中的软骨细胞时，才对它们进行免疫染色。骨关节炎软骨细胞培养上清液中金属蛋白酶活性明显高于对照组，免疫印迹法鉴定为基质金属蛋白酶-3，而基质金属蛋白酶组织抑制因子含量明显低于对照组。大多数骨性关节炎滑膜衬里细胞也有表达(20/23，87%)，且与滑膜炎症细胞浸润积分呈正相关，而在正常滑膜中未见表达。光镜和电子显微镜研究表明，基质金属蛋白酶-3能消化人关节软骨中的蛋白多糖聚集体。用肿瘤坏死因子-α和/或白介素1-α处理正常和骨关节炎软骨切片，可增加基质金属蛋白酶-3免疫反应软骨细胞的数量和染色强度。这些结果提示，软骨细胞和滑膜衬里细胞在这些细胞因子的刺激下产生的基质金属蛋白酶-3可能在人骨关节软骨蛋白多糖的降解中起重要作用。
Degradation of proteoglycans is an initial change in osteoarthritic cartilage. Matrix metalloproteinase-3 (MMP-3; stromelysin) capable of degrading cartilage proteoglycans and type IX collagen was immunolocalized in osteoarthritic and normal cartilage. Immunohistochemical studies showed MMP-3 in chondrocytes of the superficial and transition zones in approximately 90% of osteoarthritic cartilage (60 of 67 samples) and in 31% of those of the superficial zone in some normal cartilage (4 of 13 samples). MMP-3 staining correlated directly with the histological histochemical scores of Mankin and with proteoglycan depletion, up to a certain grade of severity. Chondrocytes in the deep radial zone, clusters, and osteophytes were immunostained only when proteoglycan depletion and fissures affected them. Culture media from osteoarthritic cartilage contained significantly higher levels of metalloproteinase activity that was identified as MMP-3 by immunoblotting and lower amounts of tissue inhibitor of metalloproteinases compared with those in the control samples. MMP-3 was also immunolocalized in the lining cells of most osteoarthritic synovium (20 of 23 specimens, 87%) with a direct correlation with scores of inflammatory cell infiltration in the synovium, but it was not detected in the normal synovium. Light and electron microscopic studies demonstrated that MMP-3 digests proteoglycan aggregates in human articular cartilage. Treatment of normal and osteoarthritic cartilage slices with tumor necrosis factor-alpha and/or interleukin-1 alpha increased the number of MMP-3-immunoreactive chondrocytes and the intensity of the staining. These data suggest that MMP-3 produced by the chondrocytes and synovial lining cells under stimulation with these cytokines may be important in proteoglycan degradation in human ostoearthritic cartilage.