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Cited by 29Adenosine and Purinergic SignalingOral microbiology and periodontitis researchBone Metabolism and Diseases

Adenosine triphosphate stimulates RANKL expression through P2Y1receptor-cyclo-oxygenase-dependent pathway in human periodontal ligament cells

Luckprom, P., Wongkhantee, S., Yongchaitrakul, T., Pavasant, P.·2010·Journal of Periodontal Research
DOI 10.1111/j.1600-0765.2009.01256.x
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Abstract

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 microm). 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 kappaB (NF kappaB) inhibitor, pyrrolidine dithiocarbamate, inhibited RANKL expression, prostaglandin E(2) production and NF kappaB 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 kappaB 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 kappaB-COX-RANKL axis in periodontal tissue.

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Authors
Luckprom, P., Wongkhantee, S., Yongchaitrakul, T., & Pavasant, P.
Affiliations
  • Chulalongkorn University (TH)
  • Khon Kaen University (TH)
Corresponding author
Pavasant, P.
ORCID
Pavasant, P.
Venue
Journal of Periodontal Research
Publisher
Wiley
Published
2010-06
Volume
45
Issue
3
Pages
404-411
ISSN
  • 0022-3484 (ISSN-L)
  • 1600-0765
DOI
10.1111/j.1600-0765.2009.01256.x
OpenAlex
W2098166758
Cited by
29
References
26
Citations by year
2025: 2 · 2023: 2 · 2022: 2 · 2020: 1 · 2019: 1 · 2018: 3 · 2017: 2 · 2015: 5 · 2014: 2 · 2013: 1 · 2012: 5
FWCI
1.97
Type
journal article
Language
en
Open access
closed
Licence
doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 1918 d)
Locations
  • Journal of Periodontal Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Chulalongkorn University
  • Thailand Research Fund
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
  • Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Keywords
adenosine triphosphate, RANKL expression, P2Y1 receptor, cyclooxygenase-2, prostaglandin E2, periodontal ligament cells, mechanical stress, protein kinase A, NF-κB, bone resorption, bone homeostasis, extracellular ATP signaling
MeSH terms
Adenosine Diphosphate, Adenosine Triphosphate, Biomechanical Phenomena, Bone Resorption, Cells, Cultured, Enzyme Inhibitors, Estrenes, Humans, Indomethacin, Isoquinolines, Periodontal Ligament, Phosphodiesterase Inhibitors, Type C Phospholipases, Pyrrolidines, Pyrrolidinones, Sulfonamides, Thiocarbamates, Dinoprostone, NF-kappa B, Bone Remodeling, Cyclic AMP-Dependent Protein Kinases, Receptors, Purinergic P2, RNA, Small Interfering, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, RANK Ligand, Receptors, Purinergic P2Y1, Purinergic P2 Receptor Antagonists

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