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It causes deterioration of the oral environments and leads to the pathogenesis of various systemic diseases. However, the molecular mechanisms and risk factors for RRR progression are still unclear and controversial. In this study, we developed a tooth extraction model using mice for analyzing long-term morphological and gene expression changes in the alveolar bone. We further applied ovariectomy to this model to elucidate the effects of osteoporosis on RRR progression. As a result, the alveolar bone loss was biphasic and consisted of rapid loss in the early stages and subsequently slow and sustained bone loss over a long period. Histological analysis indicated that ovariectomy prolonged the activation of osteoclasts in the alveolar bone. Furthermore, the expressions of\n                    <jats:italic>Tnfsf11<\/jats:italic>\n                    and\n                    <jats:italic>Sema4d<\/jats:italic>\n                    kept increasing for a long time in OVX mice. Administration of neutralization antibodies for receptor activator of NF-\u03baB ligand (RANKL) effectively suppressed RRR. Similarly, inhibition of Semaphorin 4D (Sema4D) also improved alveolar bone loss. This study demonstrated that reduced ovarian function may be a risk factor for RRR and that RANKL and Sema4D suppression are potential treatments.\n                  <\/jats:p>","DOI":"10.1038\/s41598-022-08016-3","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T10:02:44Z","timestamp":1646733764000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Inhibition of RANKL and Sema4D improves residual ridge resorption in mice"],"prefix":"10.1038","volume":"12","author":[{"given":"Meri","family":"Hisamoto","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunsuke","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Iwata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshihiko","family":"Iwanaga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsuro","family":"Yokoyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,3,8]]},"reference":[{"key":"8016_CR1","unstructured":"Survey of Dental Disease in 2016 by the ministry of Health, Labor and Welfare in Japan. https:\/\/www.mhlw.go.jp\/toukei\/list\/62-28.html (2016)."},{"key":"8016_CR2","unstructured":"Center for Disease Control and Prevention, US Dept of Health and Human Services https:\/\/www.cdc.gov\/oralhealth\/fast-facts\/tooth-loss\/index.html (2019)."},{"issue":"2","key":"8016_CR3","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1177\/154405910408300216","volume":"83","author":"M Mogi","year":"2004","unstructured":"Mogi, M., Otogoto, J., Ota, N. & Togari, A. 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