{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T12:14:03Z","timestamp":1789733643393,"version":"4.0.1"},"reference-count":133,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T00:00:00Z","timestamp":1618531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DE021921"],"award-info":[{"award-number":["R01DE021921"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Schoenleber Pilot Grant from the University of Pennsylvania School of Dental Medicine","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Orthodontic Faculty Development Fellowship Award from the American Association of Orthodontists Foundation (HHJ)","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Alveolar bone remodeling in orthodontic tooth movement (OTM) is a highly regulated process that coordinates bone resorption by osteoclasts and new bone formation by osteoblasts. Mechanisms involved in OTM include mechano-sensing, sterile inflammation-mediated osteoclastogenesis on the compression side and tensile force-induced osteogenesis on the tension side. Several intracellular signaling pathways and mechanosensors including the cilia and ion channels transduce mechanical force into biochemical signals that stimulate formation of osteoclasts or osteoblasts. To date, many studies were performed in vitro or using human gingival crevicular fluid samples. Thus, the use of transgenic animals is very helpful in examining a cause and effect relationship. Key cell types that participate in mediating the response to OTM include periodontal ligament fibroblasts, mesenchymal stem cells, osteoblasts, osteocytes, and osteoclasts. Intercellular signals that stimulate cellular processes needed for orthodontic tooth movement include receptor activator of nuclear factor-\u03baB ligand (RANKL), tumor necrosis factor-\u03b1 (TNF-\u03b1), dickkopf Wnt signaling pathway inhibitor 1 (DKK1), sclerostin, transforming growth factor beta (TGF-\u03b2), and bone morphogenetic proteins (BMPs). In this review, we critically summarize the current OTM studies using transgenic animal models in order to provide mechanistic insight into the cellular events and the molecular regulation of OTM.<\/jats:p>","DOI":"10.3390\/jcm10081733","type":"journal-article","created":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T10:20:11Z","timestamp":1618568411000},"page":"1733","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Mechanistic Insight into Orthodontic Tooth Movement Based on Animal Studies: A Critical Review"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3928-961X","authenticated-orcid":false,"given":"Hyeran Helen","family":"Jeon","sequence":"first","affiliation":[{"name":"Department of Orthodontics, School of Dental Medicine, University of Pennsylvania, 240 South 40th Street, Philadelphia, PA 19104-6030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hellen","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School of Dental Medicine, University of Pennsylvania, 240 South 40th Street, Philadelphia, PA 19104-6030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, School of Dental Medicine, University of Pennsylvania, 240 South 40th Street, Philadelphia, PA 19104-6030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/0002-9416(67)90118-2","article-title":"Clinical and histologic observations on tooth movement during and after orthodontic treatment","volume":"53","author":"Reitan","year":"1967","journal-title":"Am. 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