title: β2-Adrenergic signal transduction plays a detrimental role in subchondral bone loss of temporomandibular joint in osteoarthritis.
abstract: The present study tested whether activation of the sympathetic tone by aberrant joint loading elicits abnormal subchondral bone remodeling in temporomandibular joint (TMJ) osteoarthritis. Abnormal dental occlusion was created in experimental rats, which were then intraperitoneally injected by saline, propranolol or isoproterenol. The norepinephrine contents, distribution of sympathetic nerve fibers, expression of β-adrenergic receptors (β-ARs) and remodeling parameters in the condylar subchondral bone were investigated. Mesenchymal stem cells (MSCs) from condylar subchondral bones were harvested for comparison of their β-ARs, pro-osteoclastic gene expressions and pro-osteoclastic function. Increases in norepinephrine level, sympathetic nerve fiber distribution and β2-AR expression were observed in the condylar subchondral bone of experimental rats, together with subchondral bone loss and increased osteoclast activity. β-antagonist (propranolol) suppressed subchondral bone loss and osteoclast hyperfunction while β-agonist (isoproterenol) exacerbated those responses. MSCs from experimental condylar subchondral bone expressed higher levels of β2-AR and RANKL; norepinephrine stimulation further increased their RANKL expression and pro-osteoclastic function. These effects were blocked by inhibition of β2-AR or the PKA pathway. RANKL expression by MSCs decreased after propranolol administration and increased after isoproterenol administration. It is concluded that β2-AR signal-mediated subchondral bone loss in TMJ osteoarthritisis associated with increased RANKL secretion by MSCs.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, Fourth Military Medical University, 145 Changle Western Road, Xi'an, China 710032.
authors.forename: Kai
authors.initials: K
authors.lastname: Jiao
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Prosthodontics, School of Stomatology, Fourth Military Medical University, Changle Western Road No.145, Xi'an, China 710032.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Niu
authors.affiliation: Department of Stomatology, Affiliated Hospital of Academy of Military Medical Science, Beijing, China.
authors.forename: Qi-hong
authors.initials: QH
authors.lastname: Li
authors.affiliation: Undergraduate Department of Oral Science, Fourth Military Medical University, Changle Western Road No.145, Xi'an, China 710032.
authors.forename: Gao-tong
authors.initials: GT
authors.lastname: Ren
authors.affiliation: Undergraduate Department of Oral Science, Fourth Military Medical University, Changle Western Road No.145, Xi'an, China 710032.
authors.forename: Chang-ming
authors.initials: CM
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, Fourth Military Medical University, 145 Changle Western Road, Xi'an, China 710032.
authors.forename: Yun-dong
authors.initials: YD
authors.lastname: Liu
authors.affiliation: College of Dental Medicine, Georgia Reagents University, Augusta, GA, USA.
authors.forename: Franklin 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, 145 Changle Western Road, Xi'an, China 710032.
authors.forename: Mei-qing
authors.initials: MQ
authors.lastname: Wang
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D001862:Bone Resorption / Q000378:metabolism* / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009638:Norepinephrine / Q000494:pharmacology; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053245:RANK Ligand / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013704:Temporomandibular Joint / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
chemical_list: D018663:Adrenergic Agents; D053245:RANK Ligand; D011943:Receptors, Adrenergic, beta; D009638:Norepinephrine