Amelioration of arthritis in two murine models using antibodies to Oncostatin M
Objective Oncostatin M (OSM) is a member of the interleukin‐6 cytokine family, with well‐documented effects on cell growth and differentiation. OSM also has proinflammatory and cartilage degradative properties. The aim of this study was to investigate the significance of OSM in arthritis pathology u...
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Published in | Arthritis and rheumatism Vol. 44; no. 11; pp. 2697 - 2702 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
John Wiley & Sons, Inc
01.11.2001
Wiley |
Subjects | |
Online Access | Get full text |
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Summary: | Objective
Oncostatin M (OSM) is a member of the interleukin‐6 cytokine family, with well‐documented effects on cell growth and differentiation. OSM also has proinflammatory and cartilage degradative properties. The aim of this study was to investigate the significance of OSM in arthritis pathology using a neutralizing antibody in arthritis models.
Methods
Collagen‐induced arthritis (CIA) was established in male DBA/1 mice. Reverse transcriptase–polymerase chain reaction was used to detect OSM messenger RNA (mRNA) message levels in arthritic joints. Neutralizing anti‐OSM antibody or control immunoglobulin was administered on days 1 and 3 after disease onset. Animals were assessed for clinical arthritis for 2 weeks, followed by a histologic analysis of paws. Pristane‐induced arthritis (PIA) was produced in male CBA mice dosed with anti‐OSM or control immunoglobulin immediately before disease onset. Mice with PIA were assessed for clinical arthritis over a period of 100 days.
Results
Levels of mRNA for OSM, but not GAPDH, were elevated in arthritic joints of mice with CIA compared with those of normal controls. Mice with CIA treated with anti‐OSM antibody showed significant amelioration of both the clinical severity (P < 0.01) and the number of affected paws (P < 0.01) compared with control animals. Histologic analysis confirmed these clinical findings, revealing a marked reduction in cellular infiltration of synovium and cartilage damage. In the PIA model, the incidence of arthritis was 65% in the control group compared with 0% in the anti‐OSM–treated animals.
Conclusion
These results demonstrate a key role for endogenously produced OSM as a potent mediator of joint pathology, and suggest that OSM might be a potentially important, novel therapeutic target for treatment of established rheumatoid arthritis. |
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Bibliography: | Dr. Plater‐Zyberk and Ms Buckton contributed equally to this work. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0004-3591 1529-0131 |
DOI: | 10.1002/1529-0131(200111)44:11<2697::AID-ART450>3.0.CO;2-# |