title: Conditional Deletion of Fgfr3 in Chondrocytes leads to Osteoarthritis-like Defects in Temporomandibular Joint of Adult Mice.
abstract: Osteoarthritis (OA) in the temporomandibular joint (TMJ) is a common degenerative disease in adult, which is characterized by progressive destruction of the articular cartilage. To investigate the role of FGFR3 in the homeostasis of TMJ cartilage during adult stage, we generated Fgfr3(f/f); Col2a1-CreER(T2) (Fgfr3 cKO) mice, in which Fgfr3 was deleted in chondrocytes at 2 months of age. OA-like defects were observed in Fgfr3 cKO TMJ cartilage. Immunohistochemical staining and quantitative real-time PCR analyses revealed a significant increase in expressions of COL10, MMP13 and AMAMTS5. In addition, there was a sharp increase in chondrocyte apoptosis at the Fgfr3 cKO articular surface, which was accompanied by a down-regulation of lubricin expression. Importantly, the expressions of RUNX2 and Indian hedgehog (IHH) were up-regulated in Fgfr3 cKO TMJ. Primary Fgfr3 cKO chondrocytes were treated with IHH signaling inhibitor, which significantly reduced expressions of Runx2, Col10, Mmp13 and Adamts5. Furthermore, the IHH signaling inhibitor partially alleviated OA-like defects in the TMJ of Fgfr3 cKO mice, including restoration of lubricin expression and improvement of the integrity of the articular surface. In conclusion, our study proposes that FGFR3/IHH signaling pathway plays a critical role in maintaining the homeostasis of TMJ articular cartilage during adult stage.
authors.affiliation: Center of Bone Metabolism and Repair, Department of Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Siru
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Center of Bone Metabolism and Repair, Department of Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Yangli
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Military Nursing, School of Nursing, Third Military Medical University, Chongqing 400042, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Center of Bone Metabolism and Repair, Department of Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Junlan
authors.initials: J
authors.lastname: Huang
authors.affiliation: Center of Bone Metabolism and Repair, Department of Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Zuqiang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Center of Bone Metabolism and Repair, Department of Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Junzhou
authors.initials: J
authors.lastname: Tang
authors.affiliation: Center of Bone Metabolism and Repair, Department of Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Center of Bone Metabolism and Repair, Department of Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Xianding
authors.initials: X
authors.lastname: Sun
authors.affiliation: Center of Bone Metabolism and Repair, Department of Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Qiaoyan
authors.initials: Q
authors.lastname: Tan
authors.affiliation: Center of Bone Metabolism and Repair, Department of Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Huang
authors.affiliation: Center of Bone Metabolism and Repair, Department of Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Fengtao
authors.initials: F
authors.lastname: Luo
authors.affiliation: Center of Bone Metabolism and Repair, Department of Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Xu
authors.affiliation: Center of Bone Metabolism and Repair, Department of Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wu
authors.affiliation: Center of Bone Metabolism and Repair, Department of Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Center of Bone Metabolism and Repair, Department of Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Hangang
authors.initials: H
authors.lastname: Chen
authors.affiliation: Center of Bone Metabolism and Repair, Department of Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Su
authors.affiliation: Center of Bone Metabolism and Repair, Department of Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Du
authors.affiliation: Center of Bone Metabolism and Repair, Department of Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Center of Bone Metabolism and Repair, Department of Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology*; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D015398:Signal Transduction; D013704:Temporomandibular Joint / Q000378:metabolism / Q000473:pathology*
chemical_list: D053823:Hedgehog Proteins; C514061:ihh protein, mouse; C496366:Fgfr3 protein, mouse; D051498:Receptor, Fibroblast Growth Factor, Type 3