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Receptor activator of nuclear factor-\u03baB ligand (RANKL) is essential for this process although its cellular source in response to orthodontic forces has not been determined. Orthodontic tooth movement is considered to be an aseptic inflammatory process that is stimulated by leukocytes including T and B lymphocytes which are presumed to stimulate bone resorption. We determined whether periodontal ligament and bone lining cells were an essential source of RANKL by tamoxifen induced deletion of RANKL in which Cre recombinase was driven by a 3.2\u2009kb reporter element of the Col1\u03b11 gene in experimental mice (Col1\u03b11.CreER<jats:sup>TM<jats:bold>+<\/jats:bold><\/jats:sup>.RANKL<jats:sup>f\/f<\/jats:sup>) and compared results with littermate controls (Col1\u03b11.CreER<jats:sup>TM\u2212<\/jats:sup>.RANKL<jats:sup>f\/f<\/jats:sup>). By examination of Col1\u03b11.CreER<jats:sup>TM+<\/jats:sup>.ROSA26 reporter mice we showed tissue specificity of tamoxifen induced Cre recombinase predominantly in the periodontal ligament and bone lining cells. Surprisingly we found that most of the orthodontic tooth movement and formation of osteoclasts was blocked in the experimental mice, which also had a reduced periodontal ligament space. Thus, we demonstrate for the first time that RANKL produced by periodontal ligament and bone lining cells provide the major driving force for tooth movement and osteoclastogenesis in response to orthodontic forces.<\/jats:p>","DOI":"10.1038\/s41368-017-0004-8","type":"journal-article","created":{"date-parts":[[2018,2,26]],"date-time":"2018-02-26T16:30:35Z","timestamp":1519662635000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["RANKL deletion in periodontal ligament and bone lining cells blocks orthodontic tooth movement"],"prefix":"10.1038","volume":"10","author":[{"given":"Chia-Ying","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeran Helen","family":"Jeon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Alshabab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Jin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Hsi","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana T.","family":"Graves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,2,26]]},"reference":[{"key":"4_CR1","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1016\/j.reuma.2011.03.003","volume":"7","author":"JA Riancho","year":"2011","unstructured":"Riancho, J. 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