title: ClC-7 Deficiency Impairs Tooth Development and Eruption.
abstract: CLCN7 gene encodes the voltage gated chloride channel 7 (ClC-7) in humans. The mutations in CLCN7 have been associated with osteopetrosis in connection to the abnormal osteoclasts functions. Previously, we found that some osteopetrosis patients with CLCN7 mutations suffered from impacted teeth and root dysplasia. Here we set up two in vivo models under a normal or an osteoclast-poor environment to investigate how ClC-7 affects tooth development and tooth eruption. Firstly, chitosan-Clcn7-siRNA nanoparticles were injected around the first maxillary molar germ of newborn mice and caused the delay of tooth eruption and deformed tooth with root dysplasia. Secondly, E13.5 molar germs infected with Clcn7 shRNA lentivirus were transplanted under the kidney capsule and presented the abnormal changes in dentin structure, periodontal tissue and cementum. All these teeth changes have been reported in the patients with CLCN7 mutation. In vitro studies of ameloblasts, odontoblasts and dental follicle cells (DFCs) were conducted to explore the involved mechanism. We found that Clcn7 deficiency affect the differentiation of these cells, as well as the interaction between DFCs and osteoclasts through RANKL/OPG pathway. We conclude that ClC-7 may affect tooth development by directly targeting tooth cells, and regulate tooth eruption through DFC mediated osteoclast pathway.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Biology, Clinic of Oral Rare and Genetic Diseases, School of Stomatology, The Fourth Military Medical University, 145 West Changle Road, Xi'an, 710032, People's Republic of China.|Department of Stomatology, Nanfang Hospital, Guangzhou; College of Stomatology, Southern Medical University, Guangzhou, 510515, People's Republic of China.
authors.forename: He
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Biology, Clinic of Oral Rare and Genetic Diseases, School of Stomatology, The Fourth Military Medical University, 145 West Changle Road, Xi'an, 710032, People's Republic of China.|State Key Laboratory of Military Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Meng
authors.initials: M
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Biology, Clinic of Oral Rare and Genetic Diseases, School of Stomatology, The Fourth Military Medical University, 145 West Changle Road, Xi'an, 710032, People's Republic of China.
authors.forename: Jinwen
authors.initials: J
authors.lastname: Ni
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Biology, Clinic of Oral Rare and Genetic Diseases, School of Stomatology, The Fourth Military Medical University, 145 West Changle Road, Xi'an, 710032, People's Republic of China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Biology, Clinic of Oral Rare and Genetic Diseases, School of Stomatology, The Fourth Military Medical University, 145 West Changle Road, Xi'an, 710032, People's Republic of China.|State Key Laboratory of Military Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Yutao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Interdisciplinary Nanoscience Center (iNANO) and Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, Denmark; Xiangya Stomatological Hospital, Central South University, Changsha 410078, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Biology, Clinic of Oral Rare and Genetic Diseases, School of Stomatology, The Fourth Military Medical University, 145 West Changle Road, Xi'an, 710032, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Biology, Clinic of Oral Rare and Genetic Diseases, School of Stomatology, The Fourth Military Medical University, 145 West Changle Road, Xi'an, 710032, People's Republic of China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Endodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Huiming
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Stomatology, Nanfang Hospital, Guangzhou; College of Stomatology, Southern Medical University, Guangzhou, 510515, People's Republic of China.
authors.forename: Buling
authors.initials: B
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Biology, Clinic of Oral Rare and Genetic Diseases, School of Stomatology, The Fourth Military Medical University, 145 West Changle Road, Xi'an, 710032, People's Republic of China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Duan
mesh_terms: D000565:Ameloblasts / Q000378:metabolism; D000818:Animals; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology; D018118:Chloride Channels / Q000172:deficiency / Q000378:metabolism*; D003804:Dentin / Q000254:growth & development; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008963:Molar / Q000254:growth & development*; D053758:Nanoparticles / Q000737:chemistry; D009804:Odontoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D034741:RNA, Small Interfering / Q000737:chemistry / Q000494:pharmacology; D014078:Tooth Eruption / Q000187:drug effects / Q000502:physiology*
chemical_list: D018118:Chloride Channels; C490803:Clcn7 protein, mouse; D034741:RNA, Small Interfering; D048271:Chitosan
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