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This article is part of the supplement: 3rd World Congress of the Global Arthritis Research Network (GARN): International Arthritis Summit

Oral presentation

Paracrine pathways of cartilage destruction in osteoarthritis

S Abramson, M Attur, M Dave, M Leung, J Patel, P Gomez and A Amin

Author Affiliations

Division of Rheumatology, NYU School of Medicine – Hospital for Joint Diseases, New York, USA

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Arthritis Res Ther 2003, 5(Suppl 3):2  doi:10.1186/ar801


The electronic version of this article is the complete one and can be found online at:


Published:12 September 2003

©

Oral presentation

Osteoarthritis (OA) has been considered a biomechanically driven, degenerative disease of cartilage. However, the OA disease process affects not only the cartilage, but also the entire joint structure; and within the bone, cartilage and synovium of affected joints, profound metabolic changes transpire, which include the production of growth factors, nitric oxide (NO), prostaglandins (PGs), leukotrienes (LTs), IL-1β, tumor necrosis factor alpha, IL-6, and IL-8. The autocrine production of IL-1β by OA cartilage has been of particular interest, since both ex vivo human and in vivo animal studies indicate that IL-1 antagonists effectively attenuate cartilage degradation. Microarray technology has demonstrated differential expression in OA cartilage of a variety of IL-1-induced, NFβB-dependent genes. Among IL-β-induced products of OA cartilage are various eicosanoids, which include E2, PGD2, LTB4, PGF, PGFand thromboxane. Treatment of OA cartilage with cyclooxygenase (COX) inhibitors increases LTB4 production threefold to fivefold, indicating shunting of arachidonate from the COX to the 5-LO pathway. Functional analyses of individual eicosanoids reveals that PGD2, in contrast to its derivative PGJ2, stimulates catabolic processes, including NO and PG production. Lipoxin and 15-epi-lipoxin are also spontaneously released by OA cartilage, where they act to inhibit the spontaneous production of NO, PGE2, IL-8 and IL-6. Consistent with the notion that OA is not simply a degenerative disease of cartilage, gene expression analysis of circulating peripheral blood mononuclear cells (PBMCs) shows upregulation of mRNA for IL-1β, COX-2, IL-6, and IL-8 in OA (but not normal) PBMCs. OA PBMCs produce threefold to fivefold more PGE2 in response to stimulation with IL-1β than do normal cells. Thus, PBMCs, like chondrocytes and synovial cells, are activated in OA, and merit evaluation as sensors of inflammatory processes in the OA joint.