Improved regeneration and de novo bone formation in a diabetic zebrafish model treated with paricalcitol and cinacalcet
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.1/13130 |
Resumo: | Bone 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. |
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Improved regeneration and de novo bone formation in a diabetic zebrafish model treated with paricalcitol and cinacalcetCalcium-sensing receptorInsulin gene-expressionChronic kidney-diseaseVitamin-d-receptorSecondary hyperparathyroidismMineral densityDialysis patientsAdult zebrafishDanio-rerioBeta-cellsBone 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.European Regional Development Fund (ERDF) through the COMPETE-Operational Competitiveness ProgramFCT-Fundacao para a Ciencia e a Tecnologia [PEst-CCMAR/Multi/04326/2013]WileySapientiaPires De Carvalho, Filipe RicardoFernandes, Ana R.Leonor Cancela, M.Gavaia, Paulo2019-11-20T15:07:37Z2017-052017-05-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.1/13130eng1067-192710.1111/wrr.12536info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-24T10:25:11Zoai:sapientia.ualg.pt:10400.1/13130Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:04:20.045226Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Improved regeneration and de novo bone formation in a diabetic zebrafish model treated with paricalcitol and cinacalcet |
title |
Improved regeneration and de novo bone formation in a diabetic zebrafish model treated with paricalcitol and cinacalcet |
spellingShingle |
Improved regeneration and de novo bone formation in a diabetic zebrafish model treated with paricalcitol and cinacalcet Pires De Carvalho, Filipe Ricardo Calcium-sensing receptor Insulin gene-expression Chronic kidney-disease Vitamin-d-receptor Secondary hyperparathyroidism Mineral density Dialysis patients Adult zebrafish Danio-rerio Beta-cells |
title_short |
Improved regeneration and de novo bone formation in a diabetic zebrafish model treated with paricalcitol and cinacalcet |
title_full |
Improved regeneration and de novo bone formation in a diabetic zebrafish model treated with paricalcitol and cinacalcet |
title_fullStr |
Improved regeneration and de novo bone formation in a diabetic zebrafish model treated with paricalcitol and cinacalcet |
title_full_unstemmed |
Improved regeneration and de novo bone formation in a diabetic zebrafish model treated with paricalcitol and cinacalcet |
title_sort |
Improved regeneration and de novo bone formation in a diabetic zebrafish model treated with paricalcitol and cinacalcet |
author |
Pires De Carvalho, Filipe Ricardo |
author_facet |
Pires De Carvalho, Filipe Ricardo Fernandes, Ana R. Leonor Cancela, M. Gavaia, Paulo |
author_role |
author |
author2 |
Fernandes, Ana R. Leonor Cancela, M. Gavaia, Paulo |
author2_role |
author author author |
dc.contributor.none.fl_str_mv |
Sapientia |
dc.contributor.author.fl_str_mv |
Pires De Carvalho, Filipe Ricardo Fernandes, Ana R. Leonor Cancela, M. Gavaia, Paulo |
dc.subject.por.fl_str_mv |
Calcium-sensing receptor Insulin gene-expression Chronic kidney-disease Vitamin-d-receptor Secondary hyperparathyroidism Mineral density Dialysis patients Adult zebrafish Danio-rerio Beta-cells |
topic |
Calcium-sensing receptor Insulin gene-expression Chronic kidney-disease Vitamin-d-receptor Secondary hyperparathyroidism Mineral density Dialysis patients Adult zebrafish Danio-rerio Beta-cells |
description |
Bone 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. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-05 2017-05-01T00:00:00Z 2019-11-20T15:07:37Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.1/13130 |
url |
http://hdl.handle.net/10400.1/13130 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1067-1927 10.1111/wrr.12536 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Wiley |
publisher.none.fl_str_mv |
Wiley |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799133279535759360 |