title: Force-induced Adrb2 in periodontal ligament cells promotes tooth movement.
abstract: The sympathetic nervous system (SNS) regulates bone resorption through β-2 adrenergic receptor (Adrb2). In orthodontic tooth movement (OTM), mechanical force induces and regulates alveolar bone remodeling. Compressive force-associated osteoclast differentiation and alveolar bone resorption are the rate-limiting steps of tooth movement. However, whether mechanical force can activate Adrb2 and thus contribute to OTM remains unknown. In this study, orthodontic nickel-titanium springs were applied to the upper first molars of rats and Adrb1/2(-/-) mice to confirm the role of SNS and Adrb2 in OTM. The results showed that blockage of SNS activity in the jawbones of rats by means of superior cervical ganglion ectomy reduced OTM distance from 860 to 540 μm after 14 d of force application. In addition, the injection of nonselective Adrb2 agonist isoproterenol activated the downstream signaling of SNS to accelerate OTM from 300 to 540 μm after 7 d of force application. Adrb1/2(-/-) mice showed significantly reduced OTM distance (19.5 μm) compared with the wild-type mice (107.6 μm) after 7 d of force application. Histopathologic analysis showed that the number of Adrb2-positive cells increased in the compressive region of periodontal ligament after orthodontic force was applied on rats. Mechanistically, mechanical compressive force upregulated Adrb2 expression in primary-cultured human periodontal ligament cells (PDLCs) through the elevation of intracellular Ca(2+) concentration. Activation of Adrb2 in PDLCs increased the RANKL/OPG ratio and promoted the peripheral blood mononuclear cell differentiation to osteoclasts in the cocultured system. Upregulation of Adrb2 in PDLCs promoted osteoclastogenesis, which accelerated OTM through Adrb2-enhanced bone resorption. In summary, this study suggests that mechanical force-induced Adrb2 activation in PDLCs contributes to SNS-regulated OTM.
authors.affiliation: Department of Orthodontics Center for Craniofacial Stem Cell Research and Regeneration.
authors.forename: H
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Orthodontics Center for Craniofacial Stem Cell Research and Regeneration.
authors.forename: X
authors.initials: X
authors.lastname: Kou
authors.affiliation: Department of Orthodontics Center for Craniofacial Stem Cell Research and Regeneration.
authors.forename: R
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of Orthodontics Center for Craniofacial Stem Cell Research and Regeneration.
authors.forename: D
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Orthodontics Center for Craniofacial Stem Cell Research and Regeneration.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Orthodontics Center for Craniofacial Stem Cell Research and Regeneration.
authors.forename: Y
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Orthodontics Center for Craniofacial Stem Cell Research and Regeneration.
authors.forename: L
authors.initials: L
authors.lastname: Feng
authors.affiliation: Department of Orthodontics Center for Craniofacial Stem Cell Research and Regeneration.
authors.forename: D
authors.initials: D
authors.lastname: He
authors.affiliation: Center for Temporomandibular Disorders and Orofacial Pain, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Gan
authors.affiliation: Department of Orthodontics Center for Craniofacial Stem Cell Research and Regeneration yanhengzhou@gmail.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000539:Alveolar Process / Q000166:cytology / Q000502:physiology; D000818:Animals; D001696:Biomechanical Phenomena; D016723:Bone Remodeling / Q000502:physiology; D001862:Bone Resorption / Q000473:pathology / Q000503:physiopathology; D020013:Calcium Signaling / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D015171:Ganglionectomy; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009969:Orthodontic Wires; D010010:Osteoclasts / Q000502:physiology; D053244:Osteoprotegerin / Q000032:analysis; D010513:Periodontal Ligament / Q000166:cytology / Q000378:metabolism*; D053245:RANK Ligand / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013314:Stress, Mechanical; D017783:Superior Cervical Ganglion / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology; D014087:Tooth Movement Techniques
chemical_list: D000318:Adrenergic beta-Agonists; D053244:Osteoprotegerin; D053245:RANK Ligand; D018343:Receptors, Adrenergic, beta-2; D007545:Isoproterenol
keywords: beta-2 adrenergic receptors; biomechanical phenomena; bone remodeling; orthodontics; osteoclast; sympathetic nervous system