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The zebrafish operculum: a powerful system to assess osteogenic bioactivities of molecules with pharmacological and toxicological relevance

2017-07Journal article Open access
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dc.contributor.authorTarasco, Marco
dc.contributor.authorLaizé, Vincent
dc.contributor.authorCardeira, João
dc.contributor.authorLeonor Cancela, M.
dc.contributor.authorGavaia, Paulo
dc.date.accessioned2019-11-20T15:07:31Z
dc.date.available2019-11-20T15:07:31Z
dc.date.issued2017-07
dc.description.abstractBone disorders affect millions of people worldwide and available therapeutics have a limited efficacy, often presenting undesirable side effects. As such, there is a need for novel molecules with bone anabolic properties. The aim of this work was to establish a rapid, reliable and reproducible method to screen for molecules with osteogenic activities, using the zebrafish operculum to assess bone formation. Exposure parameters were optimized through morphological analysis of the developing operculum of larvae exposed to calcitriol, a molecule with known pro-osteogenic properties. An exposure of 3 days initiated at 3 days post-fertilization was sufficient to stimulate operculum formation, while not affecting survival or development of the larvae. Dose dependent pro- and anti-osteogenic effects of calcitriol and cobalt chloride, respectively, demonstrated the sensitivity of the method and the suitability of the operculum system. A double transgenic reporter line expressing fluorescent markers for early and mature osteoblasts was used to gain insights into the effects of calcitriol and cobalt at the cellular level, with osteoblast maturation shown to be stimulated and inhibited, respectively, in the operculum of exposed fish. The zebrafish operculum represents a consistent, robust and rapid screening system for the discovery of novel molecules with osteogenic, anti-osteoporotic or osteotoxic activity.
dc.description.sponsorshipPortuguese Foundation for Science and Technology (FCT) [PD/BD/52425/2013, PD/00117/2012]
dc.description.sponsorshipEuropean Commission (ERDF-COMPETE) [PEst-C/MAR/LA0015/2011]
dc.description.sponsorshipFCT [UID/Multi/04326/2013, PTDC/MAR/112992/2009]
dc.identifier.doi10.1016/j.cbpc.2017.04.006
dc.identifier.issn1532-0456
dc.identifier.urihttp://hdl.handle.net/10400.1/13083
dc.language.isoeng
dc.peerreviewedyes
dc.publisherElsevier
dc.relationAQUATOX - Assessment of mineralogenic toxicity of aquatic pollutants
dc.subjectDanio-Rerio
dc.subjectBone
dc.subjectOsteocalcin
dc.subjectMineralization
dc.subjectOsteoblasts
dc.subjectOsteoporosis
dc.subjectZebrafish
dc.subjectDifferentiation
dc.subjectRegeneration
dc.subjectDisorders
dc.subjectOperculum
dc.subjectScreening
dc.subjectOsteogenesis
dc.subjectCalcitriol
dc.titleThe zebrafish operculum: a powerful system to assess osteogenic bioactivities of molecules with pharmacological and toxicological relevance
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleAQUATOX - Assessment of mineralogenic toxicity of aquatic pollutants
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F04326%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FMAR%2F112992%2F2009/PT
oaire.citation.endPage52
oaire.citation.startPage45
oaire.citation.titleComparative Biochemistry and Physiology C-Toxicology & Pharmacology
oaire.citation.volume197
oaire.fundingStream5876
oaire.fundingStream3599-PPCDT
person.familyNameTarasco
person.familyNameLaizé
person.familyNameCardeira da Silva
person.familyNameCancela
person.familyNameGavaia
person.givenNameMarco
person.givenNameVincent
person.givenNameJoão
person.givenNameM. Leonor
person.givenNamePaulo
person.identifier.ciencia-id2B1F-0392-9ABE
person.identifier.ciencia-idDC15-86F7-3AAC
person.identifier.ciencia-idB619-FC16-D007
person.identifier.orcid0000-0001-5894-6526
person.identifier.orcid0000-0001-9565-9198
person.identifier.orcid0000-0003-3722-8810
person.identifier.orcid0000-0003-3114-6662
person.identifier.orcid0000-0002-9582-1957
person.identifier.ridG-9575-2017
person.identifier.ridB-4463-2008
person.identifier.ridA-6470-2011
person.identifier.scopus-author-id57194105105
person.identifier.scopus-author-id6602982778
person.identifier.scopus-author-id55224020100
person.identifier.scopus-author-id6507104377
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
rcaap.rightsopenAccess
rcaap.typearticle
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