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Amelioration of arthritis in two murine models using antibodies to oncostatin M
C Plater-Zyberk1, J Buckton, S Thompson
1Geneva Biomedical Research Institute, Switerland.
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.
Insights
Oncostatin M (OSM) drives arthritis pathology. Neutralizing OSM with an antibody significantly reduced joint inflammation and damage in mouse models, suggesting OSM as a therapeutic target for rheumatoid arthritis.
Area of Science:
- Immunology
- Rheumatology
- Cytokine Biology
Background:
- Oncostatin M (OSM), a cytokine in the interleukin-6 family, influences cell growth and differentiation.
- OSM exhibits pro-inflammatory properties and contributes to cartilage degradation.
- The role of OSM in arthritis pathogenesis requires further investigation.
Purpose of the Study:
- To investigate the role of OSM in arthritis using a neutralizing antibody.
- To evaluate the therapeutic potential of targeting OSM in arthritis models.
Main Methods:
- Collagen-induced arthritis (CIA) and pristane-induced arthritis (PIA) mouse models were utilized.
- OSM messenger RNA (mRNA) levels in arthritic joints were assessed using reverse transcriptase-polymerase chain reaction.
- Mice were treated with anti-OSM neutralizing antibody or control immunoglobulin and evaluated for clinical and histological signs of arthritis.
Main Results:
- OSM mRNA levels were elevated in arthritic joints of CIA mice.
- Anti-OSM antibody treatment significantly reduced clinical arthritis severity and paw involvement in CIA mice.
- Histological analysis revealed reduced synovium infiltration and cartilage damage in anti-OSM treated mice.
- In the PIA model, anti-OSM treatment completely prevented arthritis incidence.
Conclusions:
- Endogenously produced OSM plays a critical role in mediating joint pathology.
- Targeting OSM with neutralizing antibodies shows promise for treating rheumatoid arthritis.
- OSM represents a potential novel therapeutic target for established rheumatoid arthritis.