E de Vrieze1, M A H J van Kessel, H M Peters, F A T Spanings, G Flik, J R Metz. 1. Department of Organismal Animal Physiology, Faculty of Science, Institute for Water and Wetland Research, Radboud University Nijmegen, Heyendaalseweg 135, 6525, AJ, Nijmegen, The Netherlands, e.devrieze@science.ru.nl.
Abstract
UNLABELLED: We demonstrate that glucocorticoids induce an osteoporotic phenotype in regenerating scales of zebrafish. Exposure to prednisolone results in altered mineral content, enhanced matrix breakdown, and an osteoporotic gene-expression profile in osteoblasts and osteoclasts. This highlights that the zebrafish scale provides a powerful tool for preclinical osteoporosis research. INTRODUCTION: This study aims to evaluate whether glucocorticoid (prednisolone) treatment of zebrafish induces an osteoporotic phenotype in regenerating scales. Scales, a readily accessible dermal bone tissue, may provide a tool to study direct osteogenesis and its disturbance by glucocorticoids. METHODS: In adult zebrafish, treated with 25 μM prednisolone phosphate via the water, scales were removed and allowed to regenerate. During regeneration scale morphology and the molar calcium/phosphorus ratio in scales were assessed and osteoblast and osteoclast activities were monitored by time profiling of cell-specific genes; mineralization was visualized by Von Kossa staining, osteoclast activity by tartrate-resistant acid phosphatase histochemistry. RESULTS: Prednisolone (compared to controls) enhances osteoclast activity and matrix resorption and slows down the build up of the calcium/phosphorus molar ratio indicative of altered crystal maturation. Prednisolone treatment further impedes regeneration through a shift in the time profiles of osteoblast and osteoclast genes that commensurates with an osteoporosis-like imbalance in bone formation. CONCLUSIONS: A glucocorticoid-induced osteoporosis phenotype as seen in mammals was induced in regenerating scalar bone of zebrafish treated with prednisolone. An unsurpassed convenience and low cost then make the zebrafish scale a superior model for preclinical studies in osteoporosis research.
UNLABELLED: We demonstrate that glucocorticoids induce an osteoporotic phenotype in regenerating scales of zebrafish. Exposure to prednisolone results in altered mineral content, enhanced matrix breakdown, and an osteoporotic gene-expression profile in osteoblasts and osteoclasts. This highlights that the zebrafish scale provides a powerful tool for preclinical osteoporosis research. INTRODUCTION: This study aims to evaluate whether glucocorticoid (prednisolone) treatment of zebrafish induces an osteoporotic phenotype in regenerating scales. Scales, a readily accessible dermal bone tissue, may provide a tool to study direct osteogenesis and its disturbance by glucocorticoids. METHODS: In adult zebrafish, treated with 25 μM prednisolone phosphate via the water, scales were removed and allowed to regenerate. During regeneration scale morphology and the molar calcium/phosphorus ratio in scales were assessed and osteoblast and osteoclast activities were monitored by time profiling of cell-specific genes; mineralization was visualized by Von Kossa staining, osteoclast activity by tartrate-resistant acid phosphatase histochemistry. RESULTS:Prednisolone (compared to controls) enhances osteoclast activity and matrix resorption and slows down the build up of the calcium/phosphorus molar ratio indicative of altered crystal maturation. Prednisolone treatment further impedes regeneration through a shift in the time profiles of osteoblast and osteoclast genes that commensurates with an osteoporosis-like imbalance in bone formation. CONCLUSIONS: A glucocorticoid-induced osteoporosis phenotype as seen in mammals was induced in regenerating scalar bone of zebrafish treated with prednisolone. An unsurpassed convenience and low cost then make the zebrafish scale a superior model for preclinical studies in osteoporosis research.
Authors: Sebastiaan A Brittijn; Suzanne J Duivesteijn; Mounia Belmamoune; Laura F M Bertens; Wilbert Bitter; Joost D de Bruijn; Danielle L Champagne; Edwin Cuppen; Gert Flik; Christina M Vandenbroucke-Grauls; Richard A J Janssen; Ilse M L de Jong; Edo Ronald de Kloet; Alexander Kros; Annemarie H Meijer; Juriaan R Metz; Astrid M van der Sar; Marcel J M Schaaf; Stefan Schulte-Merker; Herman P Spaink; Paul P Tak; Fons J Verbeek; Margriet J Vervoordeldonk; Freek J Vonk; Frans Witte; Huipin Yuan; Michael K Richardson Journal: Int J Dev Biol Date: 2009 Impact factor: 2.203
Authors: Jo Vandesompele; Katleen De Preter; Filip Pattyn; Bruce Poppe; Nadine Van Roy; Anne De Paepe; Frank Speleman Journal: Genome Biol Date: 2002-06-18 Impact factor: 13.583
Authors: K Urso; J Caetano-Lopes; P Y Lee; J Yan; K Henke; M Sury; H Liu; M Zgoda; C Jacome-Galarza; P A Nigrovic; J Duryea; M P Harris; J F Charles Journal: Bone Date: 2019-06-05 Impact factor: 4.398