title: Activation of α2A-adrenergic signal transduction in chondrocytes promotes degenerative remodelling of temporomandibular joint.
abstract: This study tested whether activation of adrenoreceptors in chondrocytes has roles in degenerative remodelling of temporomandibular joint (TMJ) and to determine associated mechanisms. Unilateral anterior crossbite (UAC) was established to induce TMJ degeneration in rats. Saline vehicle, α2- and β-adrenoreceptor antagonists or agonists were injected locally into the TMJ area of UAC rats. Cartilage degeneration, subchondral bone microarchitecture and the expression of adrenoreceptors, aggrecans, matrix metalloproteinases (MMPs) and RANKL by chondrocytes were evaluated. Chondrocytes were stimulated by norepinephrine to investigate signal transduction of adrenoreceptors. Increased α2A-adrenoreceptor expression was observed in condylar cartilage of UAC rats, together with cartilage degeneration and subchondral bone loss. Norepinephrine depresses aggrecans expression but stimulates MMP-3, MMP-13 and RANKL production by chondrocytes through ERK1/2 and PKA pathway; these effects were abolished by an α2A-adrenoreceptor antagonist. Furthermore, inhibition of α2A-adrenoreceptor attenuated degenerative remodelling in the condylar cartilage and subchondral bone, as revealed by increased cartilage thickness, proteoglycans and aggrecan expression, and decreased MMP-3, MMP-13 and RANKL expressions in cartilage, increased BMD, BV/TV, and decreased Tb.Sp in subchondral bone. Conversely, activation of α2A-adrenoreceptor intensified aforementioned degenerative changes in UAC rats. It is concluded that activation of α2A-adrenergic signal in chondrocytes promotes TMJ degenerative remodelling by chondrocyte-mediated pro-catabolic activities.
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, 710032, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Jiao
authors.affiliation: Department of Dentistry, Tangdu Hospital, Forth Military Medical University, Shannxi, Xi'an, 710038, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Zeng
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, 710032, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Niu
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, 710032, China.
authors.forename: Hong-Xu
authors.initials: HX
authors.lastname: Yang
authors.affiliation: Undergraduate Department of Oral Science, Fourth Military Medical University, Changle Western Road No.145, Xi'an, 710032, China.
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, 710032, China.
authors.forename: Xin-Yue
authors.initials: XY
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Orthodontics, School of Stomatology, Fourth Military Medical University, 145 Changle Western Road, Xi'an, 710032, China.
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Li
authors.affiliation: The Dental College of Georgia, Augusta 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, 710032, China.
authors.forename: Mei-Qing
authors.initials: MQ
authors.lastname: Wang
mesh_terms: D000322:Adrenergic Agonists / Q000494:pharmacology; D018674:Adrenergic Antagonists / Q000494:pharmacology; D053674:Aggrecans / Q000096:biosynthesis; D000818:Animals; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D008335:Mandibular Condyle / Q000502:physiology; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D009638:Norepinephrine / Q000494:pharmacology; D010003:Osteoarthritis / Q000473:pathology*; D053245:RANK Ligand / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects*; D013704:Temporomandibular Joint / Q000166:cytology / Q000378:metabolism* / Q000473:pathology*
chemical_list: C547770:Adra2a protein, rat; D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D053674:Aggrecans; D053245:RANK Ligand; D018341:Receptors, Adrenergic, alpha-2; D011943:Receptors, Adrenergic, beta; D020782:Matrix Metalloproteinases; D009638:Norepinephrine