Genetic ablation of adenosine receptor A3 results in articular cartilage degeneration
Shkhyan R., Lee S., Gullo F., Li L., Peleli M., Carlstrom M., Chagin A. S., Banks N. W., Limfat S., Liu N. Q., Evseenko D.
Journal of Molecular Medicine
Vol.96, Issue10, P. 1049-1060
Опубликовано: 2018
Тип ресурса: Статья
DOI:10.1007/s00109-018-1680-3
Аннотация:
Abstract: Osteoarthritis (OA), the most common form of arthritis, is characterized by inflammation of joints and cartilage degradation leading to disability, discomfort, severe pain, inflammation, and stiffness of the joint. It has been shown that adenosine, a purine nucleoside composed of adenine attached to ribofuranose, is enzymatically produced by the human synovium. However, the functional significance of adenosine signaling in homeostasis and pathology of synovial joints remains unclear. Adenosine acts through four cell surface receptors, i.e., A1, A2A, A2B, and A3, and here, we have systematically analyzed mice with a deficiency for A3 receptor as well as pharmacological modulations of this receptor with specific analogs. The data show that adenosine receptor signaling plays an essential role in downregulating catabolic mechanisms resulting in prevention of cartilage degeneration. Ablation of A3 resulted in development of OA in aged mice. Mechanistically, A3 signaling inhibited
Ключевые слова:
Adenosine receptor 3; Articular cartilage; CaMKII; Osteoarthritis; RUNX2
adenosine A3 receptor; adenosine A3 receptor agonist; calcium calmodulin dependent protein kinase II; transcription factor RUNX2; adenosine A3 receptor; adult; aged; animal cell; animal experiment; animal model; animal tissue; apoptosis; Article; articular cartilage; cartilage degeneration; cartilage matrix; chondrocyte; clinical article; controlled study; degradation; down regulation; female; human; human cell; human tissue; hypoosmotic stress; inflammation; male; mouse; nonhuman; osteoarthritis; protein expression; animal; articular cartilage; C57BL mouse; genetics; knockout mouse; metabolism; pathology; pig; Animals; Cartilage, Articular; Chondrocytes; Female; Humans; Male; Mice, Inbred C57BL; Mice, Knockout; Osteoarthritis; Receptor, Adenosine A3; Swine
Язык текста: Английский
ISSN: 1432-1440
Shkhyan R.
Lee S.
Gullo F.
Li L.
Peleli M.
Carlstrom M.
Chagin A. S. Andrej Stanislavovich 1976-
Banks N. W.
Limfat S.
Liu N. Q.
Evseenko D.
Шхян Р.
Лее С.
Гулло Ф.
Ли Л.
Пелели М.
Cарлстром М.
Чагин А. С. Андрей Станиславович 1976-
Банкс Н. W.
Лимфат С.
Лиу Н. Q.
Евсеенко Д.
Genetic ablation of adenosine receptor A3 results in articular cartilage degeneration
Текст визуальный непосредственный
Journal of Molecular Medicine
Springer-Verlag GmbH
Vol.96, Issue10 P. 1049-1060
2018
Статья
Adenosine receptor 3 Articular cartilage CaMKII Osteoarthritis RUNX2
adenosine A3 receptor adenosine A3 receptor agonist calcium calmodulin dependent protein kinase II transcription factor RUNX2 adenosine A3 receptor adult aged animal cell animal experiment animal model animal tissue apoptosis Article articular cartilage cartilage degeneration cartilage matrix chondrocyte clinical article controlled study degradation down regulation female human human cell human tissue hypoosmotic stress inflammation male mouse nonhuman osteoarthritis protein expression animal articular cartilage C57BL mouse genetics knockout mouse metabolism pathology pig Animals Cartilage, Articular Chondrocytes Female Humans Male Mice, Inbred C57BL Mice, Knockout Osteoarthritis Receptor, Adenosine A3 Swine
Abstract: Osteoarthritis (OA), the most common form of arthritis, is characterized by inflammation of joints and cartilage degradation leading to disability, discomfort, severe pain, inflammation, and stiffness of the joint. It has been shown that adenosine, a purine nucleoside composed of adenine attached to ribofuranose, is enzymatically produced by the human synovium. However, the functional significance of adenosine signaling in homeostasis and pathology of synovial joints remains unclear. Adenosine acts through four cell surface receptors, i.e., A1, A2A, A2B, and A3, and here, we have systematically analyzed mice with a deficiency for A3 receptor as well as pharmacological modulations of this receptor with specific analogs. The data show that adenosine receptor signaling plays an essential role in downregulating catabolic mechanisms resulting in prevention of cartilage degeneration. Ablation of A3 resulted in development of OA in aged mice. Mechanistically, A3 signaling inhibited