PMID- 20181934 OWN - NLM STAT- MEDLINE DCOM- 20100803 LR - 20211020 IS - 1530-6860 (Electronic) IS - 0892-6638 (Print) IS - 0892-6638 (Linking) VI - 24 IP - 7 DP - 2010 Jul TI - Adenosine A1 receptors (A1Rs) play a critical role in osteoclast formation and function. PG - 2325-33 LID - 10.1096/fj.09-147447 [doi] AB - Adenosine regulates a wide variety of physiological processes via interaction with one or more G-protein-coupled receptors (A(1)R, A(2A)R, A(2B)R, and A(3)R). Because A(1)R occupancy promotes fusion of human monocytes to form giant cells in vitro, we determined whether A(1)R occupancy similarly promotes osteoclast function and formation. Bone marrow cells (BMCs) were harvested from C57Bl/6 female mice or A(1)R-knockout mice and their wild-type (WT) littermates and differentiated into osteoclasts in the presence of colony stimulating factor-1 and receptor activator of NF-kappaB ligand in the presence or absence of the A(1)R antagonist 1,3-dipropyl-8-cyclopentyl xanthine (DPCPX). Osteoclast morphology was analyzed in tartrate-resistant acid phosphatase or F-actin-stained samples, and bone resorption was evaluated by toluidine blue staining of dentin. BMCs from A(1)R-knockout mice form fewer osteoclasts than BMCs from WT mice, and the A(1)R antagonist DPCPX inhibits osteoclast formation (IC(50)=1 nM), with altered morphology and reduced ability to resorb bone. A(1)R blockade increased ubiquitination and degradation of TRAF6 in RAW264.7 cells induced to differentiate into osteoclasts. These studies suggest a critical role for adenosine in bone homeostasis via interaction with adenosine A(1)R and further suggest that A(1)R may be a novel pharmacologic target to prevent the bone loss associated with inflammatory diseases and menopause. FAU - Kara, Firas M AU - Kara FM AD - Department of Medicine, Division of Clinical Pharmacology, NYU School of Medicine, 550 First Ave., New York, NY 10016, USA. FAU - Chitu, Violeta AU - Chitu V FAU - Sloane, Jennifer AU - Sloane J FAU - Axelrod, Matthew AU - Axelrod M FAU - Fredholm, Bertil B AU - Fredholm BB FAU - Stanley, E Richard AU - Stanley ER FAU - Cronstein, Bruce N AU - Cronstein BN LA - eng GR - R01 AR054897/AR/NIAMS NIH HHS/United States GR - K01 AR054486-02/AR/NIAMS NIH HHS/United States GR - R01 CA032551/CA/NCI NIH HHS/United States GR - UL1 RR029893/RR/NCRR NIH HHS/United States GR - AA13336/AA/NIAAA NIH HHS/United States GR - R37 CA026504/CA/NCI NIH HHS/United States GR - UL1RR029893/RR/NCRR NIH HHS/United States GR - R01 AR041911/AR/NIAMS NIH HHS/United States GR - R01 CA25604/CA/NCI NIH HHS/United States GR - AR41911/AR/NIAMS NIH HHS/United States GR - P30 AR046121/AR/NIAMS NIH HHS/United States GR - K01 AR054486/AR/NIAMS NIH HHS/United States GR - AR54897/AR/NIAMS NIH HHS/United States GR - P30 CA013330/CA/NCI NIH HHS/United States GR - R01 AA013336/AA/NIAAA NIH HHS/United States GR - P30 CA13330/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20100224 PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - 0 (Receptor, Adenosine A1) RN - 0 (TNF Receptor-Associated Factor 6) SB - IM MH - Animals MH - Bone Marrow Cells/cytology MH - Bone Resorption MH - Cell Differentiation MH - Cell Shape MH - Female MH - Homeostasis MH - Mice MH - Osteoclasts/*cytology/physiology MH - Receptor, Adenosine A1/*physiology MH - TNF Receptor-Associated Factor 6/metabolism PMC - PMC2887264 EDAT- 2010/02/26 06:00 MHDA- 2010/08/04 06:00 PMCR- 2011/07/01 CRDT- 2010/02/26 06:00 PHST- 2010/02/26 06:00 [entrez] PHST- 2010/02/26 06:00 [pubmed] PHST- 2010/08/04 06:00 [medline] PHST- 2011/07/01 00:00 [pmc-release] AID - fj.09-147447 [pii] AID - 09-147447 [pii] AID - 10.1096/fj.09-147447 [doi] PST - ppublish SO - FASEB J. 2010 Jul;24(7):2325-33. doi: 10.1096/fj.09-147447. Epub 2010 Feb 24.