Persistent global inflammation caused by the loss of SIRT1 protects against experimental osteoarthritis
Sacitharan P., Zarebska JM., Stott BA., Parisi I., Curtinha MST., Bou-Gharios G., Edwards J., Vincent TL.
Inflammatory pathways have been attributed to play a central role in the pathogenesis of osteoarthritis (OA). However, most previous studies using knockout (KO) mice to inactivate inflammatory genes have showed no significant protection in experimental OA. In addition, biologic treatments targeting cytokines in OA have showed poor efficacy in clinical studies. This raises the question whether persistent inflammation has a central role in driving disease. The histone deacetylase Sirtuin 1 (SIRT1) has potent anti-inflammatory effects, thought in part, by decreasing NF-kB translocation into the nucleus. In this study, we examine the disease outcome in mice in which SIRT1 has been deleted globally or just in the cartilage.