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The role of oncostatin M in animal and human connective tissue collagen turnover and its localization within the rheumatoid joint

Lookup NU author(s): Emeritus Professor Tim Cawston, Paul Koshy, Emeritus Professor Drew Rowan, Dr William Shingleton

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Abstract

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.


Publication metadata

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

Year: 1998

Volume: 41

Issue: 10

Pages: 1760-1771

Print publication date: 01/10/1998

ISSN (print): 0004-3591

ISSN (electronic): 1529-0131

Publisher: John Wiley & Sons, Inc.

URL: http://dx.doi.org/10.1002/1529-0131(199810)41:10<1760::AID-ART8>3.0.CO;2-M

DOI: 10.1002/1529-0131(199810)41:10<1760::AID-ART8>3.0.CO;2-M


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