期刊
JOURNAL OF PERIODONTAL RESEARCH
卷 45, 期 3, 页码 404-411出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1600-0765.2009.01256.x
关键词
adenosine triphosphate; cyclo-oxygenase; periodontal ligament; P2Y(1) receptor; receptor activator of nuclear factor kappa B ligand
资金
- Thailand Research Fund (TRF) [5180004]
- Chulalongkorn University
Background and Objective: Our previous study showed that human periodontal ligament cells responded to mechanical stress by increasing adenosine triphosphate (ATP) release, accompanied by the increased expression of RANKL and osteopontin. We found that the signaling pathway of mechanical stress-induced osteopontin was mediated through ATP/P2Y(1) receptor and Rho kinase activation but that of mechanical stress-induced RANKL was different. In this study, we further investigated the effect of extracellular ATP on the expression of RANKL and the mechanism involved. Material and Methods: Human periodontal ligament cells were treated with ATP (10-40 mu m). The expressions of RANKL and cyclo-oxygenase 2 (COX-2) were examined by RT-PCR and western blot analysis. The level of prostaglandin E-2 was determined using ELISA. Signaling pathways were investigated by using inhibitors and antagonist. Results: Adenosine triphosphate induced the expression of RANKL. Indomethacin, an inhibitor of COX, could abolish the induction of RANKL expression, suggesting a COX-dependent mechanism. A cAMP-dependent protein kinase inhibitor, H89, and a nuclear factor kappa B (NF kappa B) inhibitor, pyrrolidine dithiocarbamate, inhibited RANKL expression, prostaglandin E-2 production and NF kappa B translocation. In addition, a specific P2Y(1) receptor antagonist, MRS2179, and P2Y(1) small interfering RNA diminished the effect of ATP. Conclusion: Extracellular ATP stimulates RANKL expression in human periodontal ligament cells through a pathway dependent on the P2Y(1) receptor, cAMP-dependent protein kinase, NF kappa B and COX. Our results suggest that, among the molecules responsible for the effect of mechanical stress, ATP participates in bone resorption or bone homeostasis by mediating its signal through the P2Y(1) receptor and the NF kappa B-COX-RANKL axis in periodontal tissue.
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