title: Chondrocyte FGFR3 Regulates Bone Mass by Inhibiting Osteogenesis.
abstract: Chondrogenesis can regulate bone formation. Fibroblast growth factor receptor 3, highly expressed in chondrocytes, is a negative regulator of bone growth. To investigate whether chondrocyte FGFR3 regulates osteogenesis, thereby contributing to postnatal bone formation and bone remodeling, mice with conditional knock-out of Fgfr3 in chondrocytes (mutant (MUT)) were generated. MUT mice displayed overgrowth of bone with lengthened growth plates. Bone mass of MUT mice was significantly increased at both 1 month and 4 months of age. Histological analysis showed that osteoblast number and bone formation were remarkably enhanced after deletion of Fgfr3 in chondrocytes. Chondrocyte-osteoblast co-culture assay further revealed that Fgfr3 deficiency in chondrocytes promoted differentiation and mineralization of osteoblasts by up-regulating the expressions of Ihh, Bmp2, Bmp4, Bmp7, Wnt4, and Tgf-β1, as well as down-regulating Nog expression. In addition, osteoclastogenesis was also impaired in MUT mice with decreased number of osteoclasts lining trabecular bone, which may be related to the reduced ratio of Rankl to Opg in Fgfr3-deficient chondrocytes. This study reveals that chondrocyte FGFR3 is involved in the regulation of bone formation and bone remodeling by a paracrine mechanism.
authors.affiliation: From the Department of Rehabilitation Medicine, Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wen
authors.affiliation: From the Department of Rehabilitation Medicine, Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042.|the 305 Hospital of Chinese People's Liberation Army, Beijing 100017, and.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Li
authors.affiliation: From the Department of Rehabilitation Medicine, Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042.|the Department of Emergency Treatment, Lanzhou General Hospital, Lanzhou Command, Chinese People's Liberation Army, Lanzhou 730050, China.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Tang
authors.affiliation: From the Department of Rehabilitation Medicine, Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042.
authors.forename: Junzhou
authors.initials: J
authors.lastname: Tang
authors.affiliation: From the Department of Rehabilitation Medicine, Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042.
authors.forename: Siru
authors.initials: S
authors.lastname: Zhou
authors.affiliation: From the Department of Rehabilitation Medicine, Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042.
authors.forename: Yangli
authors.initials: Y
authors.lastname: Xie
authors.affiliation: From the Department of Rehabilitation Medicine, Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Guo
authors.affiliation: From the Department of Rehabilitation Medicine, Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: From the Department of Rehabilitation Medicine, Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Du
authors.affiliation: From the Department of Rehabilitation Medicine, Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, sunansyd@163.com.
authors.forename: Nan
authors.initials: N
authors.lastname: Su
authors.affiliation: From the Department of Rehabilitation Medicine, Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, linchen70@163.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis / Q000235:genetics; D016723:Bone Remodeling / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D018920:Coculture Techniques; D006132:Growth Plate / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size / Q000502:physiology; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D053244:Osteoprotegerin / Q000096:biosynthesis* / Q000235:genetics; D019899:Paracrine Communication / Q000502:physiology*; D053245:RANK Ligand / Q000096:biosynthesis / Q000235:genetics; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000096:biosynthesis* / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D060528:Wnt4 Protein / Q000096:biosynthesis / Q000235:genetics
chemical_list: D019485:Bone Morphogenetic Proteins; D053244:Osteoprotegerin; D053245:RANK Ligand; C508961:Tgfb1 protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D053773:Transforming Growth Factor beta1; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse; C496366:Fgfr3 protein, mouse; D051498:Receptor, Fibroblast Growth Factor, Type 3
keywords: FGFR3; bone; chondrocyte; co-culture; fibroblast growth factor receptor (FGFR); osteoblast; osteoclast; osteogenesis