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A model of inflammatory arthritis highlights a role for oncostatin M in pro-inflammatory cytokine-induced bone destruction via RANK/RANKL

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

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Abstract

Oncostatin M is a pro-inflammatory cytokine previously shown to promote marked cartilage destruction both in vitro and in vivo when in combination with IL-1 or tumour necrosis factor alpha. However, the in vivo effects of these potent cytokine combinations on bone catabolism are unknown. Using adenoviral gene transfer, we have overexpressed oncostatin M in combination with either IL-1 or tumour necrosis factor alpha intra-articularly in the knees of C57BL/6 mice. Both of these combinations induced marked bone damage and markedly increased tartrate-resistant acid phosphatase-positive multinucleate cell staining in the synovium and at the front of bone erosions. Furthermore, there was increased expression of RANK and its ligand RANKL in the inflammatory cells, in inflamed synovium and in articular cartilage of knee joints treated with the cytokine combinations compared with expression in joints treated with the cytokines alone or the control. This model of inflammatory arthritis demonstrates that, in vivo, oncostatin M in combination with either IL-1 or tumour necrosis factor alpha represents cytokine combinations that promote bone destruction. The model also provides further evidence that increased osteoclast-like, tartrate-resistant acid phosphatase-positive staining multinucleate cells and upregulation of RANK/ RANKL in joint tissues are key factors in pathological bone destruction.


Publication metadata

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

Publication type: Article

Publication status: Published

Journal: Arthritis Research & Therapy

Year: 2004

Volume: 7

Issue: 1

Pages: R57-R64

Print publication date: 10/11/2004

ISSN (print): 1478-6354

ISSN (electronic): 1478-6362

Publisher: BioMed Central Ltd.

URL: http://dx.doi.org/10.1186/ar1460

DOI: 10.1186/ar1460


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