STR/ort Mice, a Model for Spontaneous Osteoarthritis, Exhibit Elevated Levels of Both Local and Systemic Inflammatory Markers
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.
Document Type: Research Article
Affiliations: 1: Molecular Biology, Genzyme Corporation, Framingham, Massachusetts, USA 2: Pathology, Genzyme Corporation, Framingham, Massachusetts, USA 3: Orthopeadic Research, Genzyme Corporation, Framingham, Massachusetts, USA
Publication date: August 1, 2011
Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.
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