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Resveratrol-mediated Reversal of Doxorubicin-Induced Osteoclast differentiation

2022-12-02Journal article Open access
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dc.contributor.authorPoudel, Sunil
dc.contributor.authorMartins, Gil
dc.contributor.authorCancela, M. Leonor
dc.contributor.authorGavaia, Paulo
dc.date.accessioned2022-12-20T11:30:31Z
dc.date.available2022-12-20T11:30:31Z
dc.date.issued2022-12-02
dc.date.updated2022-12-09T20:23:22Z
dc.description.abstractSecondary osteoporosis has been associated with cancer patients undertaking Doxorubicin (DOX) chemotherapy. However, the molecular mechanisms behind DOX-induced bone loss have not been elucidated. Molecules that can protect against the adverse effects of DOX are still a challenge in chemotherapeutic treatments. We investigated the effect and mechanism of DOX in osteoclast differentiation and used the Sirt 1 activator resveratrol (RES) to counteract DOX-induced effects. RAW 264.7 cells were differentiated into osteoclasts under cotreatment with DOX and RES, alone or combined. RES treatment inhibited DOX-induced osteoclast differentiation, reduced the expression of osteoclast fusion marker Oc-stamp and osteoclast differentiation markers Rank, Trap, Ctsk and Nfatc1. Conversely, RES induced the upregulation of antioxidant genes Sod 1 and Nrf 2 while DOX significantly reduced the FoxM1 expression, resulting in oxidative stress. Treatment with the antioxidant MitoTEMPO did not influence DOX-induced osteoclast differentiation. DOX-induced osteoclastogenesis was studied using the cathepsin-K zebrafish reporter line (Tg[ctsk:DsRed]). DOX significantly increased ctsk signal, while RES cotreatment resulted in a significant reduction in ctsk positive cells. RES significantly rescued DOX-induced mucositis in this model. Additionally, DOX-exposed zebrafish displayed altered locomotor behavior and locomotory patterns, while RES significantly reversed these effects. Our research shows that RES prevents DOX-induced osteoclast fusion and activation in vitro and in vivo and reduces DOX-induced mucositis, while improving locomotion parameters.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationInternational Journal of Molecular Sciences 23 (23): 15160 (2022)pt_PT
dc.identifier.doi10.3390/ijms232315160pt_PT
dc.identifier.eissn1422-0067
dc.identifier.urihttp://hdl.handle.net/10400.1/18677
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationAlgarve Centre for Marine Sciences
dc.relationAlgarve Centre for Marine Sciences
dc.relationCentre for Marine and Environmental Research
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectOsteoclast differentiationpt_PT
dc.subjectOxidative stresspt_PT
dc.subjectResveratrolpt_PT
dc.subjectMitoTEMPOpt_PT
dc.subjectDoxorubicinpt_PT
dc.subjectSecondary osteoporosispt_PT
dc.titleResveratrol-mediated Reversal of Doxorubicin-Induced Osteoclast differentiationpt_PT
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.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.citation.issue23pt_PT
oaire.citation.startPage15160pt_PT
oaire.citation.titleInternational Journal of Molecular Sciencespt_PT
oaire.citation.volume23pt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
person.familyNamePoudel
person.familyNameMartins
person.familyNameCancela
person.familyNameGavaia
person.givenNameSunil
person.givenNameGil
person.givenNameM. Leonor
person.givenNamePaulo
person.identifier.ciencia-id8718-1C0C-CBE8
person.identifier.ciencia-idD11F-8D8A-8EA1
person.identifier.ciencia-idB619-FC16-D007
person.identifier.orcid0000-0002-3750-0071
person.identifier.orcid0000-0002-1344-2954
person.identifier.orcid0000-0003-3114-6662
person.identifier.orcid0000-0002-9582-1957
person.identifier.ridA-6470-2011
person.identifier.scopus-author-id6507104377
project.funder.identifierhttp://doi.org/10.13039/501100001871
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
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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