Coordinate synthesis of stromelysin, interleukin-1, and oncogene proteins in experimental osteoarthritis. An immunohistochemical study.
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.
Pelletier
J P
JP
University of Montreal, Rheumatic Disease Unit, Quebec, Canada.
Faure
M P
MP
DiBattista
J A
JA
Wilhelm
S
S
Visco
D
D
Martel-Pelletier
J
J
D000818:Animals; D002358:Cartilage, Articular / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004285:Dogs; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000096:biosynthesis*; D007719:Knee Joint; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D013583:Synovial Membrane / Q000737:chemistry / Q000378:metabolism / Q000473:pathology
D007375:Interleukin-1; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3