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Adenoviral gene transfer of interleukin-1 in combination with oncostatin M induces significant joint damage in a murine model

Lookup NU author(s): Emeritus Professor Drew Rowan, Emeritus Professor Tim Cawston


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Oncostatin M (OSM) is an interleukin (IL)-6 family cytokine that we have previously shown can synergize with a number of proinflammatory cytokines to promote the release of collagen from cartilage in explant culture. However, the effects of this potent cytokine combination in vivo are not known. Using adenoviral gene transfer, we have overexpressed murine IL-1 (AdmIL-1) and murine OSM (AdmOSM) intraarticularly in the knees of C57BL/6 mice. Histological analyses indicated marked synovial hyperplasia and inflammatory cell infiltration for both AdmIL-1 and AdmOSM but not in control joints. This inflammation was even more pronounced for the AdmIL-1+AdmOSM combination with evidence of cartilage and bone destruction. Significant loss of both proteoglycan and collagen was also seen for this combination, and immunohistochemistry revealed an increased expression of matrix metalloproteinases (MMPs) with decreased tissue inhibitor of metalloproteinases (TIMPs) in both articular cartilage and synovium. Similar expression profiles for MMPs/TIMPs were found in IL-1+OSM-stimulated human articular chondrocytes. Taken together, these data confirm that, in vivo, OSM can exacerbate the effects of IL-1 resulting in inflammation and tissue destruction characteristic of that seen in rheumatoid arthritis. We provide further evidence to implicate the up-regulation of MMPs as a key factor in joint pathology. (Am J Pathol 2003, 162:1975-1984)

Publication metadata

Author(s): Rowan AD, Hui W, Cawston TE, Richards CD

Publication type: Article

Publication status: Published

Journal: The American Journal of Pathology

Year: 2003

Volume: 162

Issue: 6

Pages: 1975-1984

ISSN (print): 0002-9440

ISSN (electronic): 1525-2191

Publisher: American Society for Investigative Pathology