PUBLICATION
Immune suppressive and bone inhibitory effects of prednisolone in growing and regenerating zebrafish tissues
- Authors
- Geurtzen, K., Vernet, A., Freidin, A., Rauner, M., Hofbauer, L.C., Schneider, J.E., Brand, M., Knopf, F.
- ID
- ZDB-PUB-170805-13
- Date
- 2017
- Source
- Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 32(12): 2476-2488 (Journal)
- Registered Authors
- Brand, Michael, Knopf, Franziska
- Keywords
- Animal models, Corticosteroids, Osteoblast, Osteoclast, Osteoporosis
- MeSH Terms
-
- Animals
- Bone Development/drug effects*
- Bone Regeneration/drug effects*
- Cell Proliferation/drug effects
- Cell Survival/drug effects
- Homeostasis/drug effects
- Immunosuppressive Agents/pharmacology*
- Osteoblasts/cytology
- Osteoblasts/drug effects
- Osteogenesis/drug effects
- Prednisolone/pharmacology*
- Zebrafish/physiology*
- PubMed
- 28771888 Full text @ J. Bone Miner. Res.
Citation
Geurtzen, K., Vernet, A., Freidin, A., Rauner, M., Hofbauer, L.C., Schneider, J.E., Brand, M., Knopf, F. (2017) Immune suppressive and bone inhibitory effects of prednisolone in growing and regenerating zebrafish tissues. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 32(12):2476-2488.
Abstract
Glucocorticoids are widely used as therapeutic agents to treat immune-mediated diseases in humans because of their anti-inflammatory and immunosuppressive effects. However, glucocorticoids have various adverse effects, in particular rapid and pronounced bone loss associated with fractures in glucocorticoid-induced osteoporosis, a common form of secondary osteoporosis. In zebrafish, which are increasingly used to study processes of bone regeneration and disease, glucocorticoids show detrimental effects on bone tissue; however, the underlying cellular mechanisms are incompletely understood. Here, we show that treatment with the glucocorticoid prednisolone impacts on the number, activity and differentiation of osteoblasts, osteoclasts and immune cells during ontogenetic growth, homeostasis and regeneration of zebrafish bone. Macrophage numbers are reduced in both larval and adult tissues, correlating with decreased generation of myelomonocytes and enhanced apoptosis of these cells. In contrast, osteoblasts fail to proliferate, show decreased activity and undergo incomplete differentiation. In addition, prednisolone treatment mitigates the number and recruitment of osteoclasts to sites of bone regeneration in adult fish. In combination, these effects delay bone growth and impair bone regeneration. Our study demonstrates the many-faceted effects of glucocorticoids in non-mammalian vertebrates and helps to further establish the zebrafish as a model to study glucocorticoid-induced osteoporosis. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping