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Lookup NU author(s): Emeritus Professor Tim Cawston,
Emeritus Professor Drew Rowan,
Dr William Shingleton
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Objective, To study the interaction of interleukin-1 alpha (IL-1 alpha) and oncostatin M (OSM) in promoting cartilage collagen destruction. Methods. Bovine, porcine, and human cartilage and human chondrocytes were studied in culture. The levels of collagenase (matrix metalloproteinase 1 [MMP-1]) and tissue inhibitor of metalloproteinases 1 (TIMP-1) were measured by bioassay and enzyme-linked immunosorbent assay (ELISA). The levels of OSM in rheumatoid synovial fluid were measured by ELISA. Results. When combined with OSM, IL-1 alpha, IL-1 beta, and tumor necrosis factor alpha released proteoglycan and collagen from cartilage. OSM was the only member of the IL-6 family to have this effect. Human tendon also responded to IL-1 alpha and OSM, OSM increased the production of MMP-1 and TIMP-1 but when combined with IL-1 alpha, synergistically promoted MMP-1 production in human chondrocytes and synovial fibroblasts. High levels of OSM were found in human rheumatoid synovial fluids, and confocal microscopy showed that OSM was produced by macrophages in rheumatoid synovial tissue. Conclusion, These results highlight an important new mechanism by which there is irreversible loss of collagen from cartilage.
Author(s): Cawston TE, Curry VA, Summers CA, Clark IM, Riley GP, Life PF, Spaull JR, Goldring MB, Koshy PJT, Rowan AD, Shingleton WD
Publication type: Article
Publication status: Published
Journal: Arthritis & Rheumatism
Print publication date: 01/10/1998
ISSN (print): 0004-3591
ISSN (electronic): 1529-0131
Publisher: John Wiley & Sons, Inc.
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