Intraarticular injection of liposomal adenosine reduces cartilage damage in established murine and rat models of osteoarthritis

Osteoarthritis (OA) affects nearly 10% of the population of the United States and other industrialized countries and, at present, short of surgical joint replacement, there is no therapy available that can reverse the progression of the disease OA. Adenosine, acting at its A2A receptor (A2AR), is a critical autocrine factor for maintenance of cartilage homeostasis. Here we report that injection of liposomal suspensions of a selective A2AR agonist, CGS21680, significantly reduced OA cartilage damage in a rat model of established post-traumatic OA (PTOA). Differential expression analysis of mRNA from chondrocytes harvested from knees of rats with PTOA treated with liposomal A2AR agonist revealed downregulation of genes associated with matrix degradation and upregulation of genes associated with cell proliferation as compared to liposomes alone. Overall design: Articular chondorcytes were isolated and submitted for RNA sequencing with subsequent KEGG pathway analysis to characterize drivers of OA. oPOSSUM and the flatiron database were used for transcription factor binding enrichment and tissue specific network analyses.