Targeting phosphatidylinositol-3-kinase for inhibiting maxillary bone resorption

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dc.creatorMariana de Souza Santos
dc.creatorVirginia Tereza Morais Lima
dc.creatorBarrioni Breno Rocha Barrioni
dc.creatorJuliana Priscila Vago
dc.creatorJosé Alcides Almeida de Arruda
dc.creatorPedro Henrique Dias Moura Prazeres
dc.creatorFlávio Almeida Amaral
dc.creatorTarcília Aparecida da Silva
dc.creatorSoraia Macari
dc.date.accessioned2025-05-15T19:12:22Z
dc.date.accessioned2025-09-09T00:39:19Z
dc.date.available2025-05-15T19:12:22Z
dc.date.issued2023-11
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
dc.description.sponsorshipFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
dc.format.mimetypepdf
dc.identifier.doihttps://doi.org/10.1002/jcp.31121
dc.identifier.issn1097-4652
dc.identifier.urihttps://hdl.handle.net/1843/82313
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofJournal of cellular physiology
dc.rightsAcesso Restrito
dc.subjectBone remodeling
dc.subjectMaxilla
dc.subjectTooth movement techniques
dc.subjectPhosphatidylinositol 3-kinase
dc.subjectEnzymes
dc.subjectBone resorption
dc.subjectRoot resorption
dc.subjectOsteoclasts
dc.subjectOsteoblasts
dc.subjectGene deletion
dc.subjectProteins
dc.subjectReceptor activator of nuclear factor-kappa B
dc.subjectMinerals
dc.subjectAlkaline phosphatase
dc.subjectInterleukin-6
dc.subject.otherBone remodeling
dc.subject.otherMaxilla
dc.subject.otherOrthodontic tooth movement
dc.subject.otherPhosphatidylinositol-3-kinase
dc.titleTargeting phosphatidylinositol-3-kinase for inhibiting maxillary bone resorption
dc.typeArtigo de periódico
local.citation.epage2667
local.citation.issue11
local.citation.spage2651
local.citation.volume238
local.description.resumoPrevious studies have suggested a role of phosphatidylinositol-3-kinase gamma (PI3Kγ) in bone remodeling, but the mechanism remains undefined. Here, we explored the contribution of PI3Kγ in the resorption of maxillary bone and dental roots using models of orthodontic tooth movement (OTM), orthodontic-induced inflammatory root resorption, and rapid maxillary expansion (RME). PI3Kγ-deficient mice (PI3Kγ-/- ), mice with loss of PI3Kγ kinase activity (PI3KγKD/KD ) and C57BL/6 mice treated with a PI3Kγ inhibitor (AS605240) and respective controls were used. The maxillary bones of PI3Kγ-/- , PI3KγKD/KD , 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. PI3Kγ-/- 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-related transcription factor 2 (Runx2) and alkaline phosphatase (Alp), a reduction of interleukin-6 (Il-6), as well as a lack of responsiveness of receptor activator of nuclear factor kappa-Β (Rank) in PI3Kγ-/- and PI3KγKD/KD mice compared to control mice. The maxillary bones of PI3Kγ-/- animals showed reduced p-Akt expression. In vitro, bone marrow cells treated with AS605240 and cells from PI3Kγ-/- mice exhibited significant augment of osteoblast mineralization and less osteoclast differentiation. The PI3Kγ/Akt axis is pivotal for bone remodeling by providing negative and positive signals for the differentiation of osteoclasts and osteoblasts, respectively.
local.identifier.orcidhttps://orcid.org/0000-0003-3969-1331
local.identifier.orcidhttps://orcid.org/0000-0002-8681-6451
local.identifier.orcidhttps://orcid.org/0000-0001-8188-3738
local.identifier.orcidhttps://orcid.org/0000-0002-6599-3950
local.identifier.orcidhttps://orcid.org/0000-0002-1933-3230
local.identifier.orcidhttps://orcid.org/0000-0002-1695-0612
local.identifier.orcidhttps://orcid.org/0000-0001-9623-7835
local.identifier.orcidhttps://orcid.org/0000-0001-7643-6589
local.publisher.countryBrasil
local.publisher.departmentFAO - DEPARTAMENTO DE CLÍNICA
local.publisher.departmentFAO - DEPARTAMENTO DE ODONTOLOGIA RESTAURADORA
local.publisher.departmentICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIA
local.publisher.initialsUFMG
local.url.externahttps://onlinelibrary.wiley.com/doi/10.1002/jcp.31121

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