title: 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.
authors.affiliation: Molecular Biology, Genzyme Corporation, Framingham, Massachusetts, USA. sirkka.kyostio-moore@genzyme.com
authors.forename: Sirkka
authors.initials: S
authors.lastname: Kyostio-Moore
authors.forename: Bindu
authors.initials: B
authors.lastname: Nambiar
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hutto
authors.forename: Patty J
authors.initials: PJ
authors.lastname: Ewing
authors.forename: Susan
authors.initials: S
authors.lastname: Piraino
authors.forename: Patricia
authors.initials: P
authors.lastname: Berthelette
authors.forename: Cathleen
authors.initials: C
authors.lastname: Sookdeo
authors.forename: Gloria
authors.initials: G
authors.lastname: Matthews
authors.forename: Donna
authors.initials: D
authors.lastname: Armentano
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D016207:Cytokines / Q000097:blood; D017127:Glycation End Products, Advanced / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism; D007150:Immunohistochemistry; D007596:Joints / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology
chemical_list: D015415:Biomarkers; D016207:Cytokines; D017127:Glycation End Products, Advanced; D024243:HMGB1 Protein