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Zebrafish as a model to unveil the Pro-Osteogenic effects of Boron-Vitamin D3 synergism

2022Journal article Open Access
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dc.contributor.authorSojan, Jerry Maria
dc.contributor.authorGundappa, Manu Kumar
dc.contributor.authorCarletti, Alessio
dc.contributor.authorGaspar, Vasco
dc.contributor.authorGavaia, Paulo
dc.contributor.authorMaradonna, Francesca
dc.contributor.authorCarnevali, Oliana
dc.date.accessioned2022-10-25T09:21:27Z
dc.date.available2022-10-25T09:21:27Z
dc.date.issued2022
dc.description.abstractThe micronutrient boron (B) plays a key role during the ossification process as suggested by various in vitro and in vivo studies. To deepen our understanding of the molecular mechanism involved in the osteogenicity of B and its possible interaction with vitamin D3 (VD), wild-type AB zebrafish (Danio rerio) were used for morphometric analysis and transcriptomic analysis in addition to taking advantage of the availability of specific zebrafish osteoblast reporter lines. First, osteoactive concentrations of B, VD, and their combinations were established by morphometric analysis of the opercular bone in alizarin red-stained zebrafish larvae exposed to two selected concentrations of B (10 and 100 ng/ml), one concentration of VD (10 pg/ml), and their respective combinations. Bone formation, as measured by opercular bone growth, was significantly increased in the two combination treatments than VD alone. Subsequently, a transcriptomic approach was adopted to unveil the molecular key regulators involved in the synergy. Clustering of differentially expressed genes revealed enrichment toward bone and skeletal functions in the groups co-treated with B and VD. Downstream analysis confirmed mitogen-activated protein kinase as the most regulated pathway by the synergy groups in addition to transforming growth factor-beta signaling, focal adhesion, and calcium signaling. The best-performing synergistic treatment, B at 10 ng/ml and VD at 10 pg/ml, was applied to two zebrafish transgenic lines, Tg(sp7:mCherry) and Tg(bglap:EGFP), at multiple time points to further explore the results of the transcriptomic analysis. The synergistic treatment with B and VD induced enrichment of intermediate (sp7(+)) osteoblast at 6 and 9 days post fertilization (dpf) and of mature (bglap(+)) osteoblasts at 15 dpf. The results obtained validate the role of B in VD-dependent control over bone mineralization and can help to widen the spectrum of therapeutic approaches to alleviate pathological conditions caused by VD deficiency by using low concentrations of B as a nutritional additive.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.3389/fnut.2022.868805pt_PT
dc.identifier.issn2296-861X
dc.identifier.urihttp://hdl.handle.net/10400.1/18422
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherFrontiers Mediapt_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.subjectBonept_PT
dc.subjectBoronpt_PT
dc.subjectVitamin Dpt_PT
dc.subjectMicronutrientspt_PT
dc.subjectZebrafishpt_PT
dc.subjectRNA-Seqpt_PT
dc.subjectTransgenic linespt_PT
dc.subjectCell differentiationpt_PT
dc.titleZebrafish as a model to unveil the Pro-Osteogenic effects of Boron-Vitamin D3 synergismpt_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.titleFrontiers in Nutritionpt_PT
oaire.citation.volume9pt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
person.familyNameGundappa
person.familyNameCarletti
person.familyNameGavaia
person.givenNameManu Kumar
person.givenNameAlessio
person.givenNamePaulo
person.identifier.ciencia-idBE18-E938-C489
person.identifier.ciencia-idB619-FC16-D007
person.identifier.orcid0000-0003-4328-2178
person.identifier.orcid0000-0003-2593-2499
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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