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Updated: May 25, 2026
The Monoiodoacetate Model of Osteoarthritis Pain in the Mouse
Published on: May 16, 2016
STR/ort mice, a model for spontaneous osteoarthritis, exhibit elevated levels of both local and systemic inflammatory
Sirkka Kyostio-Moore1, Bindu Nambiar, Elizabeth Hutto
1Molecular Biology, Genzyme Corporation, Framingham, Massachusetts, USA. sirkka.kyostio-moore@genzyme.com
Abstract:
Osteoarthritis is a common joint disease that currently lacks disease-modifying treatments. Development of therapeutic agents for osteoarthritis requires better understanding of the disease and cost-effective in vivo models that mimic the human disease. Here, we analyzed the joints of STR/ort mice, a model for spontaneous osteoarthritis, for levels of inflammatory and oxidative stress markers and measured serum cytokines to characterize the local and systemic inflammatory status of these mice. Markers of low-grade inflammatory and oxidative stress-RAGE, AGE, S100A4, and HMGB1-were evaluated through immunohistochemistry. Of these, AGE and HMGB1 levels were elevated strongly in hyperplastic synovium, cartilage, meniscus, and ligaments in the joints of STR/ort mice compared with CBA mice, an osteoarthritis-resistant mouse strain. These increases (particularly in the synovium, meniscus, and ligaments) correlated with increased histopathologic changes in the cartilage. Serum analysis showed higher concentrations of several cytokines including IL1β, IL12p70, MIP1β, and IL5 in STR/ort mice, and these changes correlated with worsened joint morphology. These results indicate that STR/ort mice exhibited local and systemic proinflammatory conditions, both of which are present in human osteoarthritis. Therefore, the STR/ort mouse model appears to be a clinically relevant and cost-effective small animal model for testing osteoarthritis therapeutics.
Insights
The STR/ort mouse model exhibits local and systemic inflammation, mirroring human osteoarthritis. This cost-effective model is valuable for testing new osteoarthritis therapeutics.
Area of Science:
- Biomedical research
- Animal models
- Inflammation and oxidative stress
Background:
- Osteoarthritis (OA) is a prevalent joint disease with no disease-modifying treatments.
- Effective OA therapeutics require better disease understanding and cost-effective in vivo models.
- STR/ort mice spontaneously develop OA, making them a potential model.
Purpose of the Study:
- To characterize the local and systemic inflammatory status of STR/ort mice.
- To evaluate inflammatory and oxidative stress markers in STR/ort mice joints.
- To assess the suitability of STR/ort mice as a model for osteoarthritis research.
Main Methods:
- Immunohistochemistry was used to evaluate markers like RAGE, AGE, S100A4, and HMGB1 in STR/ort and CBA mice joints.
- Serum cytokines (IL1β, IL12p70, MIP1β, IL5) were measured in STR/ort mice.
- Histopathological changes in cartilage were correlated with marker levels and cytokine concentrations.
Main Results:
- Advanced glycosylation end products (AGE) and High Mobility Group protein B1 (HMGB1) were significantly elevated in STR/ort mouse joints, particularly in the synovium, meniscus, and ligaments.
- Elevated AGE and HMGB1 levels correlated with increased cartilage damage.
- STR/ort mice showed higher serum concentrations of IL1β, IL12p70, MIP1β, and IL5, correlating with worsened joint morphology.
Conclusions:
- STR/ort mice display local and systemic pro-inflammatory conditions consistent with human osteoarthritis.
- The STR/ort mouse model is a clinically relevant and cost-effective small animal model for evaluating osteoarthritis therapeutics.
