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• W2006385943 abstract "There is increasing evidence that extracellular nucleotides act on bone cells via P2 receptors. This study investigated the action of ADP and 2-methylthioADP, a potent ADP analog with selectivity for the P2Y(1) receptor, on osteoclasts, the bone-resorbing multinuclear cells. Using three different assays, we show that ADP and 2-methylthioADP at nanomolar to submicromolar levels caused up to fourfold to sixfold increases in osteoclastic bone resorption. On mature rat osteoclasts, cultured for 1 day on polished dentine disks, peak effects on resorption pit formation were observed between 20 nM and 2 microM of ADP. The same concentrations of ADP also stimulated osteoclast and resorption pit formation in 10-day mouse marrow cultures on dentine disks. In 3-day explant cultures of mouse calvarial bones, the stimulatory effect of ADP on osteoclast-mediated Ca(2+) release was greatest at 5-50 microM and equivalent to the maximal effects of prostaglandin E(2). The ADP effects were blocked in a nontoxic manner by MRS 2179, a P2Y(1) receptor antagonist. Using in situ hybridization and immunocytochemistry, we found evidence for P2Y(1) receptor expression on both osteoclasts and osteoblasts; thus, ADP could exert its actions both directly on osteoclasts and indirectly via P2Y(1) receptors on osteoblasts. As a major ATP degradation product, ADP is a novel stimulator of bone resorption that could help mediate inflammatory bone loss in vivo." @default.
• W2006385943 created "2016-06-24" @default.
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• W2006385943 date "2001-05-01" @default.
• W2006385943 modified "2023-09-26" @default.
• W2006385943 title "Extracellular ADP is a powerful osteolytic agent: evidence for signaling through the P2Y₁receptor on bone cells" @default.
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• W2006385943 doi "https://doi.org/10.1096/fj.00-0395com" @default.
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