Zebrafish scales as a new model in bone research

Researchers from the Radboud zebrafish facility have successfully collaborated with from a.o. the University of Leiden and the Hubrecht Laboratory in Utrecht within the Smartmix program. Funded by the Ministries of Economic Affairs and Education, Culture & Science, the aim of the Smarmix consortium was to develop medicines to combat diseases of the elderly affecting bones and joints. As a result of the ageing of the population, chronic diseases such as osteoporosis, rheumatoid arthritis and osteoarthritis impose an increasing threat to public health. The investigations using the zebrafish model at the Radboud zebrafish facility aimed to validate the scales of zebrafish as a novel model system in drug development. The scales of fish are bone-like plates that possess the same cell types as mammalian bone. In various collaborative research papers, we have shown (1) the similarity between zebrafish scales and human bone, (2) their susceptibility to glucocorticoid induced osteoporosis, and (3) how scales of transgenic zebrafish can be implemented in a semi high-throughput screening approach.  These results are published in highly qualified journals, such as Osteoporosis International and Bone.

1. Matrix metalloproteinases (MMPs) play an important role in remodeling of the scale plate during regeneration and this function resides in mono- and multinucleated osteoclasts. Bone 48, 704-712 (2011)

   

2. Glucocorticoids induce an osteoporotic phenotype in regenerating scales of zebrafish. This highlights that the zebrafish scale provides a powerful tool for preclinical osteoporosis research. Osteoporosis International25,  567–578 (2014)

   

   Increased osteoclast activity (red) in prednisolone-treated zebrafish scales

3. We developed and validated an ex-vivo assay, based on scales of sp7:luciferase transgenic zebrafish, through which the osteogenic effects of putative new osteoporosis drugs can be easily assessed in a 96-well plate format. Bone 74, 106-113 (2015).

   

   Schematic overview of the sp7:luciferase zebrafish model, and multi-well plate-based zebrafish scale luciferase assay.