PTHrP induces Notch signaling in periodontal ligament cells.
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.
Nakao
A
A
Department of Physiological Science and Molecular Biology, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka 814-0193, Japan.
Kajiya
H
H
Fukushima
H
H
Fukushima
A
A
Anan
H
H
Ozeki
S
S
Okabe
K
K
D016301:Alveolar Bone Loss / Q000209:etiology; D000818:Animals; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000096:biosynthesis; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism / Q000494:pharmacology; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D010010:Osteoclasts / Q000502:physiology; D044162:Parathyroid Hormone-Related Protein / Q000502:physiology*; D010513:Periodontal Ligament / Q000187:drug effects / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000378:metabolism / Q000494:pharmacology; D053245:RANK Ligand / Q000096:biosynthesis / Q000502:physiology; D051880:Receptors, Notch / Q000096:biosynthesis* / Q000737:chemistry / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012391:Root Resorption / Q000209:etiology*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction
D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D044162:Parathyroid Hormone-Related Protein; D047428:Protein Kinase Inhibitors; D053245:RANK Ligand; D051880:Receptors, Notch; D011994:Recombinant Proteins; D000072099:Serrate-Jagged Proteins; C015482:protein kinase modulator; D017868:Cyclic AMP-Dependent Protein Kinases