PUBLICATION

Novel and rapid osteoporosis model established in zebrafish using high iron stress

Authors
Zhang, W., Xu, J., Qiu, J., Xing, C., Li, X., Leng, B., Su, Y., Lin, J., Lin, J., Mei, X., Huang, Y., Meng, A., Pan, Y., Xue, Y.
ID
ZDB-PUB-180107-2
Date
2018
Source
Biochemical and Biophysical Research Communications   496(2): 654-660 (Journal)
Registered Authors
Keywords
Bone calcification, Cartilage development, High iron, Osteoporosis, Zebrafish
MeSH Terms
  • Alendronate/therapeutic use
  • Animals
  • Bone Density Conservation Agents/therapeutic use
  • Bone and Bones/drug effects
  • Bone and Bones/metabolism
  • Bone and Bones/pathology*
  • Calcification, Physiologic/drug effects
  • Disease Models, Animal
  • Iron/metabolism
  • Iron Overload/drug therapy
  • Iron Overload/metabolism*
  • Iron Overload/pathology
  • Iron Overload/physiopathology
  • Osteoblasts/drug effects
  • Osteoblasts/metabolism
  • Osteoblasts/pathology*
  • Osteogenesis/drug effects
  • Osteoporosis/drug therapy
  • Osteoporosis/metabolism*
  • Osteoporosis/pathology
  • Osteoporosis/physiopathology
  • Zebrafish*/physiology
PubMed
29305866 Full text @ Biochem. Biophys. Res. Commun.
Abstract
Osteoporosis is a global public health concern and, it can result from numerous pathogenic mechanisms, many of which are closely related with age, nutritional disorders, endocrine imbalance, or adverse drug side effects presented by glucocorticoids, heparin, and anti-epileptics. Given its wide range etiologies, it is crucial to establish an animal model of osteoporosis for use in screening potential drugs quickly and effectively. Previous research has reported that an accumulation of elevated iron in the body is an independent risk factor for osteoporosis. As such, we sought to use both zebrafish larvae and adults to model an osteoporosis phenotype using high iron stress (FAC, ferric ammonium citrate). Skeletal staining results suggested that iron-overload caused a significant decrease in bone calcification as well as severe developmental cartilage defects. In addition, osteoblast and cartilage-specific mRNA expression levels were downregulated after exposure to a high-iron environment. Most importantly, we demonstrated in both larval and adult fish that high iron-induced osteogenic defects were significantly rescued using alendronate (AL), a drug known to be effective against to human osteoporosis. Even more, the repair effect of AL was achieved by facilitating osteoblast differentiation and targeting Bmp signaling. Taken together, our findings propose an rapid and effective osteoporosis model, which could be used widely for future osteoporosis drug screening.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping