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Epigenetic regulation of ZNF687 by miR-142a-3p and DNA methylation during osteoblast differentiation and mice bone development and aging

2025-02-27Journal article Open access
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dc.contributor.authorDomingos Varela, Débora Cristina
dc.contributor.authorDomingos Varela, Tatiana da Conceição
dc.contributor.authorConceição, Natércia
dc.contributor.authorCancela, M. Leonor
dc.date.accessioned2025-04-03T10:21:20Z
dc.date.available2025-04-03T10:21:20Z
dc.date.issued2025-02-27
dc.description.abstractZinc finger protein 687 (ZNF687), a transcription factor implicated in osteoblast/osteoclast differentiation and linked to Paget's disease of bone, has unclear mechanisms in bone metabolism. Epigenetic disruptions can affect bone cell activity and contribute to bone-related diseases. This work aimed to elucidate the regulatory role of epigenetics in modulating Zfp687 expression throughout osteoblast differentiation and bone growth/aging in mice. Differentiation of the mouse-derived osteoblast precursor cell line (MC3T3-E1) showed increased expression of osteogenic markers and decreased Zfp687 expression. In the hindlimb bones of C57BL/6J mice, the expression of most bone-forming genes decreased from youth to adulthood, while Zfp687 and Runx2 expression was maintained, being only significantly reduced in old mice in comparison to young mice. Bisulfite sequencing revealed hypomethylation of the Zfp687 promoter during MC3T3-E1 differentiation and bone growth/aging. Bioinformatics predicted miR-142a-3p, miR-122b-5p, and miR-124-3p binding sites in Zfp687 3 ' UTR, and RT-qPCR analysis showed higher expression of these miRNAs in mature osteoblasts. Transfection of a miR-142-3p mimic reduced luciferase activity in the wildtype Zfp687 3 ' UTR but not the mutant 3 ' UTR and downregulated the Zfp687 gene and protein levels. In conclusion, miR-142a-3p directly targets the Zfp687 3 ' UTR, promoting its downregulation during osteoblastogenesis. Furthermore, DNA methylation does not appear to regulate Zfp687 during osteoblast differentiation or bone development in mice.eng
dc.identifier.doi10.3390/ijms26052069
dc.identifier.issn1422-0067
dc.identifier.urihttp://hdl.handle.net/10400.1/26968
dc.language.isoeng
dc.peerreviewedyes
dc.publisherMDPI
dc.relationAlgarve Centre for Marine Sciences
dc.relationAlgarve Centre for Marine Sciences
dc.relationCentre for Marine and Environmental Research
dc.relationEpigenetic regulation of ZNF687 in bone cells: elucidation of its role in the progression of Paget’s disease towards giant cell tumor of bone
dc.relationIdentification of novel CDKL5 molecular targets/pathways associated with skeletal defects present in CDKL5 associated disorders
dc.relation.ispartofInternational Journal of Molecular Sciences
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectOsteoblast differentiation
dc.subjectZNF687
dc.subjectEpigenetics
dc.subjectmiRNAs
dc.subjectDNA methylation
dc.subjectBone
dc.titleEpigenetic regulation of ZNF687 by miR-142a-3p and DNA methylation during osteoblast differentiation and mice bone development and agingeng
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleAlgarve Centre for Marine Sciences
oaire.awardTitleAlgarve Centre for Marine Sciences
oaire.awardTitleCentre for Marine and Environmental Research
oaire.awardTitleEpigenetic regulation of ZNF687 in bone cells: elucidation of its role in the progression of Paget’s disease towards giant cell tumor of bone
oaire.awardTitleIdentification of novel CDKL5 molecular targets/pathways associated with skeletal defects present in CDKL5 associated disorders
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04326%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04326%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/LA%2FP%2F0101%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F141918%2F2018/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBD%2F144230%2F2019/PT
oaire.citation.issue5
oaire.citation.startPage2069
oaire.citation.titleInternational Journal of Molecular Sciences
oaire.citation.volume26
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamOE
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
person.familyNameDomingos Varela
person.familyNameDomingos Varela
person.familyNameConceição
person.familyNameCancela
person.givenNameDébora Cristina
person.givenNameTatiana da Conceição
person.givenNameNatércia
person.givenNameM. Leonor
person.identifier.ciencia-id9A1C-DFE4-98C9
person.identifier.ciencia-idF613-7482-6731
person.identifier.ciencia-id7C11-760D-F425
person.identifier.orcid0000-0002-5057-0912
person.identifier.orcid0000-0003-3114-6662
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
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project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
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