Pelletier J P, Faure M P, DiBattista J A, Wilhelm S, Visco D, Martel-Pelletier J
University of Montreal, Rheumatic Disease Unit, Quebec, Canada.
Am J Pathol. 1993 Jan;142(1):95-105.
Metalloproteases appear to play an important role in the pathophysiology of osteoarthritis (OA) and their expression is believed to be regulated by cytokines such as interleukin-1 (IL-1). Nuclear oncogene products are suggested as mediators through which IL-1 induces metalloprotease gene expression. Little data are available on the in vivo involvement of these agents in the pathophysiology of OA. This study examined by immunohistochemistry, using specific antibodies, the distribution of stromelysin, IL-1 alpha, IL-1 beta, and oncogene products (c-FOS, c-JUN, and c-MYC) in synovium and cartilage from normal and experimental canine models of OA. In the OA synovium, stromelysin and IL-1 were localized in the cytoplasm of superficial synovial lining cells, infiltrating mononuclear cells, and endothelial and smooth muscle cells of the blood vessels, whereas oncoproteins were detected predominantly in the synovial lining cells. Normal synovial membranes demonstrated low levels of specific staining in synovial lining cells with occasional staining of blood vessel cells for IL-1 alpha, IL-1 beta, and stromelysin. In OA cartilage, chondrocytes at the superficial and middle layers as well as in fibrillated areas were found to be involved in the synthesis of stromelysin, IL-1, and oncoproteins. Diffuse staining of stromelysin and IL-1 beta in OA cartilage matrix was also identified. In normal cartilage, only a few chondrocytes at the superficial layer showed a low level of antigens. These results demonstrate the in vivo concomitant cellular and/or matrical presence of stromelysin, IL-1, and oncogene proteins in tissues from experimentally induced OA with the most intense staining at the sites of cartilage erosion and synovial proliferation. These findings suggest that they may be involved in the pathophysiology of OA, and that the regulatory mechanisms involved in the expression of these proteins may be associated.
金属蛋白酶似乎在骨关节炎（OA）的病理生理学中发挥重要作用，并且其表达被认为受细胞因子如白细胞介素-1（IL-1）调节。核癌基因产物被认为是IL-1诱导金属蛋白酶基因表达的介质。关于这些因子在OA病理生理学中的体内作用，目前可用的数据很少。本研究通过免疫组织化学，使用特异性抗体，检测了正常和实验性犬OA模型的滑膜和软骨中基质溶解素、IL-1α、IL-1β和癌基因产物（c-FOS、c-JUN和c-MYC）的分布。在OA滑膜中，基质溶解素和IL-1定位于表层滑膜衬里细胞、浸润的单核细胞以及血管的内皮和平滑肌细胞的细胞质中，而癌蛋白主要在滑膜衬里细胞中检测到。正常滑膜在滑膜衬里细胞中显示低水平的特异性染色，血管细胞偶尔有IL-1α、IL-1β和基质溶解素的染色。在OA软骨中，表层和中层以及纤维化区域的软骨细胞被发现参与基质溶解素、IL-1和癌蛋白的合成。还发现OA软骨基质中基质溶解素和IL-1β的弥漫性染色。在正常软骨中，只有表层的少数软骨细胞显示低水平的抗原。这些结果表明，在实验诱导的OA组织中，基质溶解素、IL-1和癌基因蛋白在体内同时存在于细胞和/或基质中，在软骨侵蚀和滑膜增生部位染色最强。这些发现表明它们可能参与OA的病理生理学，并且这些蛋白质表达所涉及的调节机制可能相关。
