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Improved regeneration and de novo bone formation in a diabetic zebrafish model treated with paricalcitol and cinacalcet

2017-05Journal article Open access
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dc.contributor.authorPires De Carvalho, Filipe Ricardo
dc.contributor.authorFernandes, Ana R.
dc.contributor.authorLeonor Cancela, M.
dc.contributor.authorGavaia, Paulo
dc.date.accessioned2019-11-20T15:07:37Z
dc.date.available2019-11-20T15:07:37Z
dc.date.issued2017-05
dc.description.abstractBone changes related to diabetes have been well stablished, but few strategies have been developed to prevent this growing health problem. In our work, we propose to investigate the effects of calcitriol as well as of a vitamin D analog (paricalcitol) and a calcimimetic (cinacalcet), in fin regeneration and de novo mineralization in a zebrafish model of diabetes. Following exposure of diabetic transgenic Tg(ins: nfsb-mCherry) zebrafish to calcitriol, paricalcitol and cinacalcet, caudal fins were amputated to assess their effects on tissue regeneration. Caudal fin mineralized and regenerated areas were quantified by in vivo alizarin red staining. Quantitative real-time PCR was performed using RNA from the vertebral column. Diabetic fish treated with cinacalcet and paricalcitol presented increased regenerated and mineralized areas when compared with non-treated diabetic group, while no significant increase was observed in nondiabetic fish treated with both drugs. Gene expression analysis showed an up-regulation for runt-related transcription factor 2b (runx2b), bone gamma-carboxyglutamic acid-containing protein (bglap), insulin a (insa) and insulin b (insb) and a trend of increase for sp7 transcription factor (sp7) in diabetic groups treated with cinacalcet and paricalcitol. Expression of insra and vdra was up-regulated in both diabetic and nondiabetic fish treated with cinacalcet. In nondiabetic fish treated with paricalcitol and cinacalcet a similar increase in gene expression could be observed but not so pronounced. The increased mineralization and regeneration in diabetic zebrafish treated with cinacalcet and paricalcitol can be explained by increased osteoblastic differentiation and increased insulin expression indicating pro-osteogenic potential of both drugs.
dc.description.sponsorshipEuropean Regional Development Fund (ERDF) through the COMPETE-Operational Competitiveness Program
dc.description.sponsorshipFCT-Fundacao para a Ciencia e a Tecnologia [PEst-CCMAR/Multi/04326/2013]
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1111/wrr.12536
dc.identifier.issn1067-1927
dc.identifier.issn1524-475X
dc.identifier.urihttp://hdl.handle.net/10400.1/13130
dc.language.isoeng
dc.peerreviewedyes
dc.publisherWiley
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectCalcium-sensing receptor
dc.subjectInsulin gene-expression
dc.subjectChronic kidney-disease
dc.subjectVitamin-d-receptor
dc.subjectSecondary hyperparathyroidism
dc.subjectMineral density
dc.subjectDialysis patients
dc.subjectAdult zebrafish
dc.subjectDanio-rerio
dc.subjectBeta-cells
dc.titleImproved regeneration and de novo bone formation in a diabetic zebrafish model treated with paricalcitol and cinacalcet
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F76429%2F2011/PT
oaire.citation.endPage442
oaire.citation.issue3
oaire.citation.startPage432
oaire.citation.titleWound Repair and Regeneration
oaire.citation.volume25
oaire.fundingStreamSFRH
person.familyNamePires de Carvalho
person.familyNameCancela
person.familyNameGavaia
person.givenNameFilipe Ricardo
person.givenNameM. Leonor
person.givenNamePaulo
person.identifier.ciencia-id181A-A440-7D6E
person.identifier.ciencia-idB619-FC16-D007
person.identifier.orcid0000-0002-1468-0305
person.identifier.orcid0000-0003-3114-6662
person.identifier.orcid0000-0002-9582-1957
person.identifier.ridA-6470-2011
person.identifier.scopus-author-id55115644400
person.identifier.scopus-author-id6507104377
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccess
rcaap.typearticle
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