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PTHrP Induces Notch Signaling in Periodontal Ligament Cells

¹ Department of Physiological Science and Molecular Biology, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka 814-0193, Japan;
² Department of Oral and Maxillofacial Surgery, Fukuoka Dental College, Fukuoka 814-0193, Japan;
³ Department of Bioscience, Kyushu Dental College, Kitakyushu 803-8580, Japan; and
⁴ Department of Odontology, Fukuoka Dental College, Fukuoka 814-0193, Japan

Correspondence: ^* kajiya{at}college.fdcnet.ac.jp

Periodontal ligament (PDL) cells are known to play important roles in tooth eruption and alveolar bone metabolism. We previously reported that PTHrP increases RANKL expression in human PDL cells, suggesting that it promotes odontoclastic root resorption during tooth eruption. While it is known that Notch-related genes play a key role during bone development, the role of the Notch signaling pathway in PDL cells during tooth and bone resorption is less clear. We hypothesized that PTHrP induces a Notch ligand in PDL cells and thereby regulates osteo- and odontoclastogenesis. We found that PTHrP increased Notch1 ligand Jagged1 expression in human PDL cells in a dose- and time-dependent manner. PTHrP-induced Jagged1 up-regulation was mediated by PKA activation, but not by PKC. Jagged1 also promoted RANKL-induced osteoclastogenesis. These results demonstrate that PTHrP induces Jagged1 expression in PDL cells, leading to osteo- and odontoclastogenesis, and thus likely promoting tooth and alveolar bone resorption.

Key Words: PTHrP • periodontal ligament • Jagged1 • PKA

Abbreviations: PTHrP, parathyroid-hormone-related protein • PTH/PTHrP type 1 receptor, PTH1R • RANKL, receptor activator of NF-B ligand • OPG, osteoprotegerin • PDL, periodontal ligament • TRAP, tartrate-resistant acid phosphatase • PKA, protein kinase A • PKC, protein kinase C

Journal of Dental Research, Vol. 88, No. 6, 551-556 (2009)
DOI: 10.1177/0022034509337899


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