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Here, we explored the contribution of PI3K\u03b3 in the resorption of maxillary bone and dental roots using models of orthodontic tooth movement (OTM), orthodontic\u2010induced inflammatory root resorption, and rapid maxillary expansion (RME). PI3K\u03b3\u2010deficient mice (PI3K\u03b3<jats:sup>\u2212\/\u2212<\/jats:sup>), mice with loss of PI3K\u03b3 kinase activity (PI3K\u03b3<jats:sup>KD\/KD<\/jats:sup>) and C57BL\/6 mice treated with a PI3K\u03b3 inhibitor (AS605240) and respective controls were used. The maxillary bones of PI3K\u03b3<jats:sup>\u2212\/\u2212<\/jats:sup>, PI3K\u03b3<jats:sup>KD\/KD<\/jats:sup>, and C57BL\/6 mice treated with AS605240 showed an improvement of bone quality compared to their controls, resulting in reduction of the OTM and RME in all experimental groups. PI3K\u03b3<jats:sup>\u2212\/\u2212<\/jats:sup> mice exhibited increased root volume and decreased odontoclasts counts. Consistently, the pharmacological blockade or genetic deletion of PI3K resulted in increased numbers of osteoblasts and reduction in osteoclasts during OTM. There was an augmented expression of Runt\u2010related transcription factor 2 (<jats:italic>Runx2<\/jats:italic>) and alkaline phosphatase (<jats:italic>Alp<\/jats:italic>), a reduction of interleukin\u20106 (<jats:italic>Il\u20106<\/jats:italic>), as well as a lack of responsiveness of receptor activator of nuclear factor kappa\u2010\u0392 (<jats:italic>Rank<\/jats:italic>) in PI3K\u03b3<jats:sup>\u2212\/\u2212<\/jats:sup> and PI3K\u03b3<jats:sup>KD\/KD<\/jats:sup> mice compared to control mice. The maxillary bones of PI3K\u03b3<jats:sup>\u2212\/\u2212<\/jats:sup> animals showed reduced p\u2010Akt expression. In vitro, bone marrow cells treated with AS605240 and cells from PI3K\u03b3<jats:sup>\u2212\/\u2212<\/jats:sup> mice exhibited significant augment of osteoblast mineralization and less osteoclast differentiation. The PI3K\u03b3\/Akt axis is pivotal for bone remodeling by providing negative and positive signals for the differentiation of osteoclasts and osteoblasts, respectively.<\/jats:p>","DOI":"10.1002\/jcp.31121","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T03:22:56Z","timestamp":1697080976000},"page":"2651-2667","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting phosphatidylinositol\u20103\u2010kinase for inhibiting maxillary bone resorption"],"prefix":"10.1002","volume":"238","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3969-1331","authenticated-orcid":false,"given":"Mariana de S.","family":"Santos","sequence":"first","affiliation":[{"name":"Department of Morphology Biological Science Institute, Universidade Federal de Minas Gerais Belo Horizonte Minas Gerais Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virg\u00ednia T. M.","family":"Lima","sequence":"additional","affiliation":[{"name":"Department of Restorative Dentistry Faculty of Dentistry, Universidade Federal de Minas Gerais Belo Horizonte Minas Gerais Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8681-6451","authenticated-orcid":false,"given":"Breno R.","family":"Barrioni","sequence":"additional","affiliation":[{"name":"Department of Metallurgical and Materials Engineering Faculty of Engineering, Universidade Federal de Minas Gerais Belo Horizonte Minas Gerais Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8188-3738","authenticated-orcid":false,"given":"Juliana P.","family":"Vago","sequence":"additional","affiliation":[{"name":"Department of Morphology Biological Science Institute, Universidade Federal de Minas Gerais Belo Horizonte Minas Gerais Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6599-3950","authenticated-orcid":false,"given":"Jos\u00e9 Alcides A.","family":"de Arruda","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery, Pathology and Clinical Dentistry Faculty of Dentistry, Universidade Federal de Minas Gerais Belo Horizonte Minas Gerais Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1933-3230","authenticated-orcid":false,"given":"Pedro D.","family":"Prazeres","sequence":"additional","affiliation":[{"name":"Department of Pathology Biological Science Institute, Universidade Federal de Minas Gerais Belo Horizonte Minas Gerais Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1695-0612","authenticated-orcid":false,"given":"Fl\u00e1vio A.","family":"Amaral","sequence":"additional","affiliation":[{"name":"Department of Morphology Biological Science Institute, Universidade Federal de Minas Gerais Belo Horizonte Minas Gerais Brazil"},{"name":"Department of Biochemistry and Immunology Biological Science Institute, Universidade Federal de Minas Gerais Belo Horizonte Minas Gerais Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9623-7835","authenticated-orcid":false,"given":"Tarc\u00edlia A.","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery, Pathology and Clinical Dentistry Faculty of Dentistry, Universidade Federal de Minas Gerais Belo Horizonte Minas Gerais Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7643-6589","authenticated-orcid":false,"given":"Soraia","family":"Macari","sequence":"additional","affiliation":[{"name":"Department of Morphology Biological Science Institute, Universidade Federal de Minas Gerais Belo Horizonte Minas Gerais Brazil"},{"name":"Department of Restorative Dentistry Faculty of Dentistry, Universidade Federal de Minas Gerais Belo Horizonte Minas Gerais Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,10,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.17179\/excli2019-1997"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2020.104820"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0129-z"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom9090402"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-022-00582-5"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.15229"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0014-5793(03)00055-3"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2014.04.012"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.238709.114"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)81883-8"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200401138"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.01505"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2819"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2003.09.005"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4744"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2020.109880"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-11-0175"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S148457"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5455.1049"},{"key":"e_1_2_9_21_1","doi-asserted-by":"crossref","unstructured":"Kang H. 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