title: FGFR3 Deficiency Causes Multiple Chondroma-like Lesions by Upregulating Hedgehog Signaling.
abstract: Most cartilaginous tumors are formed during skeletal development in locations adjacent to growth plates, suggesting that they arise from disordered endochondral bone growth. Fibroblast growth factor receptor (FGFR)3 signaling plays essential roles in this process; however, the role of FGFR3 in cartilaginous tumorigenesis is not known. In this study, we found that postnatal chondrocyte-specific Fgfr3 deletion induced multiple chondroma-like lesions, including enchondromas and osteochondromas, adjacent to disordered growth plates. The lesions showed decreased extracellular signal-regulated kinase (ERK) activity and increased Indian hedgehog (IHH) expression. The same was observed in Fgfr3-deficient primary chondrocytes, in which treatment with a mitogen-activated protein kinase (MEK) inhibitor increased Ihh expression. Importantly, treatment with an inhibitor of IHH signaling reduced the occurrence of chondroma-like lesions in Fgfr3-deficient mice. This is the first study reporting that the loss of Fgfr3 function leads to the formation of chondroma-like lesions via downregulation of MEK/ERK signaling and upregulation of IHH, suggesting that FGFR3 has a tumor suppressor-like function in chondrogenesis.
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, 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, China.
authors.forename: Yangli
authors.initials: Y
authors.lastname: Xie
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, 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, 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, China.
authors.forename: Qizhao
authors.initials: Q
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, 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, 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, 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, China.
authors.forename: Quan
authors.initials: Q
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, 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, 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, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Biochemistry, Rush University Medical Center, Chicago, Illinois, United States of America.
authors.forename: Di
authors.initials: D
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, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism; D002812:Chondroma / Q000235:genetics / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D053823:Hedgehog Proteins; C514061:ihh protein, mouse; C496366:Fgfr3 protein, mouse; D051498:Receptor, Fibroblast Growth Factor, Type 3