Anales RANF

S20-03 ADENOSINE METABOLISM AND RECEPTORS IN OSTEOARTHRITIS: TARGETING A2A RECEPTORS TO REVERSE INFLAMMAGING B.N. Cronstein NYU School of Medicine, New York, NY, USA Aging and injury often lead to chronic low-grade inflammation, a condition known as Inflammaging, which contributes to the development of disease in the musculoskeletal system and is also thought to contribute to the development of diabetes and other diseases of aging. Previous studies demonstrate that chondrocytes from osteoarthritic cartilage have lower cellular ATP levels, lower biomass and diminished mitochondrial function and we have discovered that this leads to diminished ATP transport into the extracellular space resulting in lower extracellular adenosine levels. In other experiments we found that reduced extracellular adenosine levels or loss of A2A receptors (A2AR) lead to the development of premature osteoarthritis (OA). Intra- articular injection of liposomal adenosine or CGS21680 (A2AR agonist) both prevents development of OA after trauma in rats, an effect completely reversed by intra-articular injection of an A2AR antagonist (ZM241385), and reverses post-traumatic OA in rats and obesity-induced OA in mice. A2AR stimulation promotes chondrocyte homeostasis and reverses OA by multiple mechanisms which will be reviewed.