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The mutations in <jats:italic>CLCN7<\/jats:italic> have been associated with osteopetrosis in connection to the abnormal osteoclasts functions. Previously, we found that some osteopetrosis patients with <jats:italic>CLCN7<\/jats:italic> mutations suffered from impacted teeth and root dysplasia. Here we set up two <jats:italic>in vivo<\/jats:italic> models under a normal or an osteoclast-poor environment to investigate how ClC-7 affects tooth development and tooth eruption. Firstly, chitosan-<jats:italic>Clcn7<\/jats:italic>-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 <jats:italic>Clcn7<\/jats:italic> 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 <jats:italic>CLCN7<\/jats:italic> mutation. <jats:italic>In vitro<\/jats:italic> studies of ameloblasts, odontoblasts and dental follicle cells (DFCs) were conducted to explore the involved mechanism. We found that <jats:italic>Clcn7<\/jats:italic> 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.<\/jats:p>","DOI":"10.1038\/srep19971","type":"journal-article","created":{"date-parts":[[2016,2,1]],"date-time":"2016-02-01T10:24:47Z","timestamp":1454322287000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["ClC-7 Deficiency Impairs Tooth Development and Eruption"],"prefix":"10.1038","volume":"6","author":[{"given":"He","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinwen","family":"Ni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanli","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiming","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Buling","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohong","family":"Duan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,2,1]]},"reference":[{"key":"BFsrep19971_CR1","doi-asserted-by":"crossref","first-page":"E1071","DOI":"10.1002\/humu.21167","volume":"31","author":"A Pangrazio","year":"2010","unstructured":"Pangrazio, A. et al. 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