title: Norepinephrine Regulates Condylar Bone Loss via Comorbid Factors.
abstract: Degenerative changes of condylar subchondral bone occur frequently in temporomandibular disorders. Although psychologic stresses and occlusal abnormalities have been implicated in temporomandibular disorder, it is not known if these risks represent synergistic comorbid factors that are involved in condylar subchondral bone degradation that is regulated by the sympathetic nervous system. In the present study, chronic immobilization stress (CIS), chemical sympathectomy, and unilateral anterior crossbite (UAC) were sequentially applied in a murine model. Norepinephrine contents in the subjects' serum and condylar subchondral bone were detected by ELISA; bone and cartilage remodeling parameters and related gene expression in the subchondral bone were examined. Subchondral bone loss and increased subchondral bone norepinephrine level were observed in the CIS and UAC groups. These groups exhibited decreased bone mineral density, volume fraction, and bone formation rate; decreased expressions of osterix, collagen I, and osteocalcin; but increased trabecular separation, osteoclast number and surface, and RANKL expression. Combined CIS + UAC produced more severe subchondral bone loss, higher bone norepinephrine level, and decreased chondrocyte density and cartilage thickness when compared to CIS or UAC alone. Sympathectomy simultaneously prevented subchondral bone loss and decreased bone norepinephrine level in all experimental subgroups when compared to the vehicle-treated counterparts. Norepinephrine also decreased mRNA expression of osterix, collagen I, and osteocalcin by mesenchymal stem cells at 7 and 14 d of stimulation and increased the expression of RANKL and RANKL/OPG ratio by mesenchymal stem cells at 2 h. In conclusion, CIS and UAC synergistically promote condylar subchondral bone loss and cartilage degradation; such processes are partially regulated by norepinephrine within subchondral bone.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: K
authors.initials: K
authors.lastname: Jiao
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Prosthodontics, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: L
authors.initials: L
authors.lastname: Niu
authors.affiliation: Undergraduate Department of Oral Science, Fourth Military Medical University, Xi'an, China.
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, Fourth Military Medical University, Xi'an, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Undergraduate Department of Oral Science, Fourth Military Medical University, Xi'an, China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: College of Dental Medicine, Georgia Reagents University, Augusta, GA, USA.
authors.forename: F R
authors.initials: FR
authors.lastname: Tay
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, Fourth Military Medical University, Xi'an, China mqwang@fmmu.edu.cn ftay@gru.edu.
authors.forename: M
authors.initials: M
authors.lastname: Wang
mesh_terms: D000818:Animals; D015519:Bone Density / Q000502:physiology; D001862:Bone Resorption / Q000209:etiology* / Q000378:metabolism; D002358:Cartilage, Articular / Q000473:pathology; D002452:Cell Count; D018929:Cell Culture Techniques; D019902:Chondrocytes / Q000473:pathology; D024042:Collagen Type I / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D007103:Immobilization; D008310:Malocclusion / Q000150:complications; D008335:Mandibular Condyle / Q000737:chemistry / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000032:analysis / Q000097:blood / Q000502:physiology*; D015675:Osteocalcin / Q000032:analysis; D010010:Osteoclasts / Q000473:pathology; D010012:Osteogenesis / Q000502:physiology; D053244:Osteoprotegerin / Q000032:analysis; D053245:RANK Ligand / Q000032:analysis; D012307:Risk Factors; D013315:Stress, Psychological / Q000503:physiopathology; D013563:Sympathectomy, Chemical / Q000379:methods; D013705:Temporomandibular Joint Disorders / Q000209:etiology* / Q000378:metabolism; D014157:Transcription Factors / Q000032:analysis
chemical_list: D024042:Collagen Type I; D053244:Osteoprotegerin; D053245:RANK Ligand; C495181:Sp7 protein, rat; C506032:Tnfrsf11b protein, rat; D014157:Transcription Factors; D015675:Osteocalcin; D009638:Norepinephrine
keywords: occlusal abnormalities; psychological stresses; subchondral bone; sympathetic nerve system (SNS); temporomandibular disorder (TMD); temporomandibular joint (TMJ)