PUBLICATION
The zebrafish operculum: a powerful system to assess osteogenic bioactivities of molecules with pharmacological and toxicological relevance
- Authors
- Tarasco, M., Laizé, V., Cardeira, J., Leonor Cancela, M., Gavaia, P.J.
- ID
- ZDB-PUB-170502-12
- Date
- 2017
- Source
- Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 197: 45-52 (Journal)
- Registered Authors
- Keywords
- Calcitriol, Operculum, Osteogenesis, Screening, Zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Calcification, Physiologic/drug effects
- Calcitriol/pharmacology
- Cobalt/toxicity
- Dose-Response Relationship, Drug
- Drug Evaluation, Preclinical/methods*
- Female
- Genetic Markers
- Larva/drug effects
- Larva/growth & development
- Male
- Osteoblasts/drug effects
- Osteogenesis/drug effects*
- Skull/drug effects
- Skull/growth & development*
- Toxicity Tests/methods*
- Zebrafish*/genetics
- PubMed
- 28457946 Full text @ Comp. Biochem. Physiol. C Toxicol. Pharmacol.
Citation
Tarasco, M., Laizé, V., Cardeira, J., Leonor Cancela, M., Gavaia, P.J. (2017) The zebrafish operculum: a powerful system to assess osteogenic bioactivities of molecules with pharmacological and toxicological relevance. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP. 197:45-52.
Abstract
Bone 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 3days initiated at 3days 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping