Arachidonic acid enhances turnover of the dermal skeleton: studies on zebrafish scales

PLoS One. 2014 Feb 19;9(2):e89347. doi: 10.1371/journal.pone.0089347. eCollection 2014.


In fish nutrition, the ratio between omega-3 and omega-6 poly-unsaturated fatty acids influences skeletal development. Supplementation of fish oils with vegetable oils increases the content of omega-6 fatty acids, such as arachidonic acid in the diet. Arachidonic acid is metabolized by cyclooxygenases to prostaglandin E2, an eicosanoid with effects on bone formation and remodeling. To elucidate effects of poly-unsaturated fatty acids on developing and existing skeletal tissues, zebrafish (Danio rerio) were fed (micro-) diets low and high in arachidonic acid content. Elasmoid scales, dermal skeletal plates, are ideal to study skeletal metabolism in zebrafish and were exploited in the present study. The fatty acid profile resulting from a high arachidonic acid diet induced mild but significant increase in matrix resorption in ontogenetic scales of adult zebrafish. Arachidonic acid affected scale regeneration (following removal of ontogenetic scales): mineral deposition was altered and both gene expression and enzymatic matrix metalloproteinase activity changed towards enhanced osteoclastic activity. Arachidonic acid also clearly stimulates matrix metalloproteinase activity in vitro, which implies that resorptive effects of arachidonic acid are mediated by matrix metalloproteinases. The gene expression profile further suggests that arachidonic acid increases maturation rate of the regenerating scale; in other words, enhances turnover. The zebrafish scale is an excellent model to study how and which fatty acids affect skeletal formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animal Structures / drug effects
  • Animal Structures / physiology*
  • Animals
  • Arachidonic Acid / pharmacology*
  • Calcium / metabolism
  • Dermis / drug effects
  • Dermis / physiology*
  • Dinoprostone / metabolism
  • Gene Expression Profiling
  • Matrix Metalloproteinases / metabolism
  • Phosphorus / metabolism
  • Regeneration / drug effects
  • Zebrafish / physiology*


  • Arachidonic Acid
  • Phosphorus
  • Matrix Metalloproteinases
  • Dinoprostone
  • Calcium

Grant support

This study was financed by the Norwegian Research Council (project number NFR 185177/S40) and the SmartMix Programme of the Netherlands Ministry of Economic Affairs and the Netherlands Ministry of Education, Culture and Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.