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

Autor: Corciulo C; Division of Translational Medicine, Department of Medicine, NYU School of Medicine, 550 First Avenue, New York, NY, 10016, USA., Castro CM; Division of Translational Medicine, Department of Medicine, NYU School of Medicine, 550 First Avenue, New York, NY, 10016, USA., Coughlin T; Department of Orthopedic Surgery, NYU School of Medicine, 550 First Avenue, New York, NY, 10016, USA., Jacob S; Institute for Systems Genetics, NYU School of Medicine, 435 East 30th Street, New York, NY, 10016, USA.; Department of Biochemistry and Molecular Pharmacology, NYU School of Medicine, 435 East 30th Street, New York, NY, 10016, USA., Li Z; Institute for Systems Genetics, NYU School of Medicine, 435 East 30th Street, New York, NY, 10016, USA.; Department of Biochemistry and Molecular Pharmacology, NYU School of Medicine, 435 East 30th Street, New York, NY, 10016, USA., Fenyö D; Institute for Systems Genetics, NYU School of Medicine, 435 East 30th Street, New York, NY, 10016, USA.; Department of Biochemistry and Molecular Pharmacology, NYU School of Medicine, 435 East 30th Street, New York, NY, 10016, USA., Rifkin DB; Department of Cell Biology, NYU School of Medicine, 550 First Avenue, New York, NY, 10016, USA., Kennedy OD; Department of Orthopedic Surgery, NYU School of Medicine, 550 First Avenue, New York, NY, 10016, USA.; Department of Anatomy, The Royal College of Surgeons in Ireland, 123 St Stephens Green, Dublin 2, Ireland., Cronstein BN; Division of Translational Medicine, Department of Medicine, NYU School of Medicine, 550 First Avenue, New York, NY, 10016, USA. bruce.cronstein@nyumc.org.; Division of Rheumatology, Department of Medicine, NYU School of Medicine, 550 First Avenue, New York, NY, 10016, USA. bruce.cronstein@nyumc.org.; Medical Science Building, NYU Langone Health, 550 1st Avenue, New York, NY, 10016, USA. bruce.cronstein@nyumc.org.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2020 Aug 10; Vol. 10 (1), pp. 13477. Date of Electronic Publication: 2020 Aug 10.
DOI: 10.1038/s41598-020-68302-w
Abstrakt: 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. Adenosine, acting at its A2A receptor (A2AR), is a critical autocrine factor for maintenance of cartilage homeostasis and here we report that injection of liposomal suspensions of either adenosine or a selective A2AR agonist, CGS21680, significantly reduced OA cartilage damage in a murine model of obesity-induced OA. The same treatment also improved swelling and preserved cartilage in the affected knees 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. Studies in vitro and in affected joints demonstrated that A2AR ligation increased the nuclear P-SMAD2/3/P-SMAD1/5/8 ratio, a change associated with repression of terminal chondrocyte differentiation. These results strongly suggest that targeting the A2AR is an effective approach to treat OA.
Databáze: MEDLINE
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