{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:55:16Z","timestamp":1786978516824,"version":"build-2736575974"},"reference-count":49,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T00:00:00Z","timestamp":1622678400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81660524"],"award-info":[{"award-number":["81660524"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Fluoride is a persistent environmental pollutant, and its excessive intake contributes to skeletal and dental fluorosis. The mechanisms underlying fluoride\u2010induced abnormal osteoblast proliferation and activation, which are related to skeletal fluorosis, have not yet been fully clarified. As important epigenetic regulators, microRNAs (miRNAs) participate in bone metabolism. On the basis of our previous miRNA\u2010seq results and bioinformatics analysis, this study investigated the role and specific molecular mechanism of miR\u2010486\u20103p in fluoride\u2010induced osteoblast proliferation and activation via\n                    <jats:italic>CyclinD1<\/jats:italic>\n                    . Herein, in the fluoride\u2010challenged population, we observed that miR\u2010486\u20103p expression decreased while\n                    <jats:italic>CyclinD1<\/jats:italic>\n                    and transforming growth factor (\n                    <jats:italic>TGF<\/jats:italic>\n                    )\n                    <jats:italic>\u2010\u03b21<\/jats:italic>\n                    increased, and miR\u2010486\u20103p level correlated negatively with the expression of\n                    <jats:italic>CyclinD1<\/jats:italic>\n                    and\n                    <jats:italic>TGF\u2010\u03b21<\/jats:italic>\n                    genes. Further, we verified that sodium fluoride (NaF) decreases miR\u2010486\u20103p expression in human osteoblasts and overexpression of miR\u2010486\u20103p reduces fluoride\u2010induced osteoblast proliferation and activation. Meanwhile, we demonstrated that miR\u2010486\u20103p regulates NaF\u2010induced upregulation of\n                    <jats:italic>CyclinD1<\/jats:italic>\n                    by directly targeting its 3\u2032\u2010untranslated region (3\u2032\u2010UTR). In addition, we observed that NaF activates the\n                    <jats:italic>TGF\u2010\u03b21<\/jats:italic>\n                    \/Smad2\/3\/\n                    <jats:italic>CyclinD1<\/jats:italic>\n                    axis and miR\u2010486\u20103p mediates transcriptional regulation of\n                    <jats:italic>CyclinD1<\/jats:italic>\n                    by TGF\u2010\u03b21\/Smad2\/3 signaling pathway via targeting\n                    <jats:italic>TGF\u2010\u03b21<\/jats:italic>\n                    3\u2032\u2010UTR in vitro. This study, thus, contributes significantly in revealing the mechanism of miR\u2010486\u20103p\u2010mediated\n                    <jats:italic>CyclinD1<\/jats:italic>\n                    upregulation in skeletal fluorosis and sheds new light on endemic fluorosis treatment.\n                  <\/jats:p>","DOI":"10.1002\/tox.23302","type":"journal-article","created":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T05:47:36Z","timestamp":1622785656000},"page":"1817-1828","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["<scp>miR<\/scp>\n                    \u2010486\u20103p regulates\n                    <i>CyclinD1<\/i>\n                    and promotes fluoride\u2010induced osteoblast proliferation and activation"],"prefix":"10.1002","volume":"36","author":[{"given":"Ting","family":"Ouyang","sequence":"first","affiliation":[{"name":"School of Public Health, The key Laboratory of Environmental Pollution Monitoring 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