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Pharmacol Res. 2016 Feb;104:1-8. doi: 10.1016/j.phrs.2015.12.009. Epub 2015 Dec 18.

Effects of bioactive fatty acid amide derivatives in zebrafish scale model of bone metabolism and disease.

Author information

1
Gruppo Ospedaliero San Donato Foundation, Milan, Italy.
2
Department of Biomedical and Clinical Sciences L. Sacco, University of Milan, Milan, Italy.
3
IRCCS Galeazzi Orthopedic Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
4
IRCCS Galeazzi Orthopedic Institute, Milan, Italy; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy. Electronic address: massimo.mariotti@unimi.it.

Abstract

The endocannabinoid system (which includes fatty acid derivatives, receptors, and metabolizing enzymes) is involved in a variety of physiological processes, including bone metabolism in which it regulates the function of osteoblasts and osteoclasts, as well as differentiation of their precursors. The zebrafish (Danio rerio) provides a useful animal model for bone research since zebrafish bones develop rapidly and are anatomically similar to mammalian bones. Putative orthologues and paralogs of endocannabinoid genes have recently been identified in zebrafish, demonstrating the presence of cannabinoid type 1 (CB1) and type 2 (CB2) receptors with affinity to endocannabinoid ligands. To identify therapeutic molecules potentially useful in bone-related diseases, we evaluated the in vivo effects of exposure to long-chain fatty acid amides in adult zebrafish. Using a well-established zebrafish scale model, we found that anandamide and N-linoleoylethanolamine are able to stimulate bone formation by increasing alkaline phosphatase activity in physiological conditions. In addition, they prevent the alteration of bone markers in a prednisolone-induced osteoporosis model in adult zebrafish scales, whereas their esterified forms do not. These data suggest that long-chain fatty acid amides are involved in regulating bone metabolism in zebrafish scales and that the CB2 receptor is a key mediator in this process.

KEYWORDS:

Bone; Endocannabinoid; Osteoblast; Osteoclast; Osteoporosis; Scale; Zebrafish

PMID:
26707833
DOI:
10.1016/j.phrs.2015.12.009
[Indexed for MEDLINE]

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