Short-chain fatty acids and FFAR2 as suppressors of bone resorption

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dc.creatorCarina Cristina Montalvany-Antonucci
dc.creatorIldeu Andrade Júnior
dc.creatorMauro Martins Teixeira
dc.creatorC. Mackay
dc.creatorA.T. Vieira
dc.creatorMarco Aurélio Ramirez Vinolo
dc.creatorTarcília Aparecida da Silva
dc.creatorLetícia Fernanda Duffles Rodrigues
dc.creatorJosé Alcides Almeida de Arruda
dc.creatorMarina Campos Zicker
dc.creatorS.. de Oliveira
dc.creatorSoraia Macari
dc.creatorGustavo Pompermayer Garlet
dc.creatorMila Fernandes Moreira Madeira
dc.creatorSandra Yasuyo Fukada Alves
dc.date.accessioned2025-08-07T18:05:35Z
dc.date.accessioned2025-09-09T00:34:27Z
dc.date.available2025-08-07T18:05:35Z
dc.date.issued2019-08
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
dc.format.mimetypepdf
dc.identifier.doihttps://doi.org/10.1016/j.bone.2019.05.016
dc.identifier.issn1873-2763
dc.identifier.urihttps://hdl.handle.net/1843/84181
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofBone
dc.rightsAcesso Restrito
dc.subjectBone remodeling
dc.subjectProteins
dc.subjectFatty acids, volatile
dc.subjectOsteoblasts
dc.subjectOsteoclasts
dc.subjectBone resorption
dc.subjectTooth movement techniques
dc.subjectOsteolysis, essential
dc.subjectBone and bones
dc.subjectEvaluation study
dc.subject.otherBone remodeling
dc.subject.otherFFAR2 protein
dc.subject.otherShort-chain fatty acids
dc.titleShort-chain fatty acids and FFAR2 as suppressors of bone resorption
dc.typeArtigo de periódico
local.citation.epage121
local.citation.spage112
local.citation.volume125
local.description.resumoShort-chain fatty acids (SCFAs) exert a variety of immune and metabolic functions by binding to G-protein-coupled receptors, mainly free fatty acid receptor 2 (FFAR2). However, the effects of SCFAs and FFARs on bone remodeling, especially in alveolar bone, have been less explored. In this study, we investigated the influence of the SCFA/FFAR2 axis on alveolar bone. Bone samples from wild-type (WT) and FFAR2-deficient mice (FFAR2-/-) were analyzed using micro-CT, histology and qPCR. WT and FFAR2-/- animals received a high-fiber diet (HFD) reported to increase circulating levels of SCFAs. Additionally, we analyzed the effects of SCFAs and a synthetic FFAR2 agonist, phenylacetamide-1 (CTMB), on bone cell differentiation. The participation of histone deacetylase inhibitors (iHDACs) in the effects of SCFAs was further assessed in vitro. CTMB treatment was also evaluated in vivo during orthodontic tooth movement (OTM). FFAR2-/- mice exhibited deterioration of maxillary bone parameters. Consistent with this, FFAR2-/- mice exhibited a significant increase of OTM and changes in bone cell numbers and in the expression of remodeling markers. The HFD partially reversed bone loss in the maxillae of FFAR2-/- mice. In WT mice, the HFD induced changes in the bone markers apparently favoring a bone formation scenario. In vitro, bone marrow cells from FFAR2-/- mice exhibited increased differentiation into osteoclasts, while no changes in osteoblasts were observed. In line with this, differentiation of osteoclasts was diminished by SCFAs and CTMB. Moreover, CTMB treatment significantly reduced OTM. Pretreatment of osteoclasts with iHDACs did not modify the effects of SCFAs on these cells. In conclusion, SCFAs function as regulators of bone resorption. The effects of SCFAs on osteoclasts are dependent on FFAR2 activation and are independent of the inhibition of HDACs. FFAR2 agonists may be useful to control bone osteolysis.
local.identifier.orcidhttps://orcid.org/0000-0002-4977-2752
local.identifier.orcidhttps://orcid.org/0000-0002-2921-2627
local.identifier.orcidhttps://orcid.org/0000-0002-2781-9986
local.identifier.orcidhttps://orcid.org/0000-0001-9623-7835
local.identifier.orcidhttps://orcid.org/0000-0002-6599-3950
local.identifier.orcidhttps://orcid.org/0000-0001-7643-6589
local.identifier.orcidhttps://orcid.org/0000-0002-5071-8382
local.identifier.orcidhttps://orcid.org/0000-0002-1770-9978
local.identifier.orcidhttps://orcid.org/0000-0003-1335-760X
local.identifier.orcidhttps://orcid.org/0000-0002-6589-4784
local.identifier.orcidhttps://orcid.org/0000-0002-6944-3008
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.departmentICB - DEPARTAMENTO DE FARMACOLOGIA
local.publisher.departmentICB - DEPARTAMENTO DE MICROBIOLOGIA
local.publisher.initialsUFMG
local.url.externahttps://www.sciencedirect.com/science/article/pii/S8756328219301917?via%3Dihub

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