Atorvastatin Attenuates Sox9 Joint and Cardiac Calcification in ApoE null mice

Abstract

BackgroundDegenerative joint disease is responsible for high morbidity in patients. The mechanisms of osteoarthritis and cardiac calcification are under investigation. We hypothesize that lipids may play a role via chondrogenesis.MethodsWe tested lipids with and without statins in the ApoE mouse to determine the Sox9 expression in the joints and valves. ApoE−/− mice (n=60). Group I (n=20) normal diet, Group II (n=20) 0.25% chol diet (w/w), and Group III (n=20) 0.25% (w/w) chol diet+atorv for the development of abnormal matrix synthesis in the joints over 24 weeks. The aortic valve (AVA) was examined for Bone formation and was assessed by microCT. Aortic Valve Disease was assessed by echo.ResultsThe chol diet induced bone in the AV and thickened knee joints with an increase in Sox9 and Cyclin as compared to the Control(>3‐fold(p<05). Atorvastatin attenuated all markers. Echo demonstrated a mild increase in the peak jet velocity. Masson Trichrome demonstrated a marked increase in the matrix synthesis.ConclusionWe demonstrated that chondrogenic mediated bone formation in the hypercholesterolemic aortic valves and abnormal matrix synthesis in the knee joints is attenuated with atorvastatin.