Improved regeneration and de novo bone formation in a diabetic zebrafish model treated with Paricalcitol and Cinacalcet

Carvalho, F.R., Fernandes, A.R., Cancela, M.L., Gavaia, P.J.
Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society   25(3): 432-442 (Journal)
Registered Authors
Cancela, Leonor
Diabetes, bone, calcimimetics, mineralization, vitamin D analogs, zebrafish
MeSH Terms
  • Amputation
  • Animal Fins/drug effects*
  • Animal Fins/injuries
  • Animal Fins/physiology
  • Animals
  • Calcimimetic Agents/pharmacology*
  • Cell Differentiation/drug effects
  • Cinacalcet/pharmacology*
  • Diabetes Mellitus, Experimental
  • Disease Models, Animal
  • Ergocalciferols/pharmacology*
  • Immunohistochemistry
  • Osteoblasts/drug effects*
  • Osteoblasts/metabolism
  • Osteogenesis/drug effects*
  • Osteogenesis/physiology
  • Real-Time Polymerase Chain Reaction
  • Regeneration/drug effects*
  • Regeneration/physiology
  • Zebrafish
28380670 Full text @ Wound Repair Regen.
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 to non-treated diabetic group, while no significant increase was observed in non-diabetic fish treated with both drugs. Gene expression analysis showed an upregulation 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 upregulated in both diabetic and non-diabetic fish treated with cinacalcet. In non-diabetic 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. This article is protected by copyright. All rights reserved.
Genes / Markers
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Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes