title: Neuronal TRPV1 activation regulates alveolar bone resorption by suppressing osteoclastogenesis via CGRP.
abstract: The transient receptor potential vanilloid 1 (TRPV1) channel is abundantly expressed in peripheral sensory neurons where it acts as an important polymodal cellular sensor for heat, acidic pH, capsaicin, and other noxious stimuli. The oral cavity is densely innervated by afferent sensory neurons and is a highly specialized organ that protects against infections as well as physical, chemical, and thermal stresses in its capacity as the first part of the digestive system. While the function of TRPV1 in sensory neurons has been intensively studied in other organs, its physiological role in periodontal tissues is unclear. In this study we found that Trpv1(-/-) mice developed severe bone loss in an experimental model of periodontitis. Chemical ablation of TRPV1-expressing sensory neurons recapitulated the phenotype of Trpv1(-/-) mice, suggesting a functional link between neuronal TRPV1 signaling and periodontal bone loss. TRPV1 activation in gingival nerves induced production of the neuropeptide, calcitonin gene-related peptide (CGRP), and CGRP treatment inhibited osteoclastogenesis in vitro. Oral administration of the TRPV1 agonist, capsaicin, suppressed ligature-induced bone loss in mice with fewer tartrate-resistant acid phosphatase (TRAP)-positive cells in alveolar bone. These results suggest that neuronal TRPV1 signaling in periodontal tissue is crucial for the regulation of osteoclastogenesis via the neuropeptide CGRP.
authors.affiliation: Laboratory of Periodontology and Immunology, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.|Division of Periodontology, Department of Oral Biological Science, Niigata University Faculty of Dentistry, Niigata, Japan.|Research Center for Advanced Oral Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Laboratory of Periodontology and Immunology, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.|Division of Periodontology, Department of Oral Biological Science, Niigata University Faculty of Dentistry, Niigata, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Matsuda
authors.affiliation: Laboratory of Periodontology and Immunology, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.|Division of Periodontology, Department of Oral Biological Science, Niigata University Faculty of Dentistry, Niigata, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sato
authors.affiliation: Sanford Burnham Prebys Medical Discovery Institute, NCI-Designated Cancer Center, La Jolla, CA, USA.
authors.forename: Petrus R
authors.initials: PR
authors.lastname: de Jong
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Bertin
authors.affiliation: Division of Periodontology, Department of Oral Biological Science, Niigata University Faculty of Dentistry, Niigata, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Tabeta
authors.affiliation: Laboratory of Periodontology and Immunology, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Yamazaki
mesh_terms: D000818:Animals; D001862:Bone Resorption; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D004195:Disease Models, Animal; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D010012:Osteogenesis; D010518:Periodontitis / Q000473:pathology*; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D015740:Calcitonin Gene-Related Peptide