title: Prednisolone induces osteoporosis-like phenotype in regenerating zebrafish scales.
abstract: 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.
  
  
  BACKGROUND
  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.affiliation: 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.
authors.forename: E
authors.initials: E
authors.lastname: de Vrieze
authors.forename: M A H J
authors.initials: MA
authors.lastname: van Kessel
authors.forename: H M
authors.initials: HM
authors.lastname: Peters
authors.forename: F A T
authors.initials: FA
authors.lastname: Spanings
authors.forename: G
authors.initials: G
authors.lastname: Flik
authors.forename: J R
authors.initials: JR
authors.lastname: Metz
mesh_terms: D000825:Animal Structures / Q000187:drug effects / Q000502:physiology; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000633:toxicity*; D008297:Male; D010010:Osteoclasts / Q000187:drug effects; D010024:Osteoporosis / Q000139:chemically induced* / Q000503:physiopathology; D010641:Phenotype; D011239:Prednisolone / Q000031:analogs & derivatives* / Q000633:toxicity; D012038:Regeneration; D015027:Zebrafish
chemical_list: D005938:Glucocorticoids; C009022:prednisolone phosphate; D011239:Prednisolone
references.citation: Int J Dev Biol. 2009;53(5-6):835-50
references.pmid: 19557689
references.citation: Cell Tissue Res. 1979 Nov;202(2):203-12
references.pmid: 519703
references.citation: Am J Physiol Regul Integr Comp Physiol. 2008 Mar;294(3):R711-9
references.pmid: 18077507
references.citation: FEBS Lett. 1997 Jul 7;411(1):145-8
references.pmid: 9247160
references.citation: Climacteric. 1998 Mar;1(1):72-9
references.pmid: 11907930
references.citation: Bone. 2006 May;38(5):652-61
references.pmid: 16298558
references.citation: Cell Tissue Res. 1988 Sep;253(3):597-607
references.pmid: 3052849
references.citation: Comp Biochem Physiol A Mol Integr Physiol. 2009 May;153(1):75-82
references.pmid: 19168143
references.citation: J Musculoskelet Neuronal Interact. 2004 Sep;4(3):268-75
references.pmid: 15615494
references.citation: Tissue Cell. 1989;21(3):447-62
references.pmid: 18620270
references.citation: Proc Natl Acad Sci U S A. 2012 Dec 26;109(52):21372-7
references.pmid: 23236130
references.citation: Arthritis Rheum. 2008 Jun;58(6):1674-86
references.pmid: 18512788
references.citation: Diabetes Metab Rev. 1988 Feb;4(1):17-30
references.pmid: 3278872
references.citation: Calcif Tissue Int. 2013 Apr;92(4):354-61
references.pmid: 23247536
references.citation: Bone. 2011 Apr 1;48(4):704-12
references.pmid: 21185415
references.citation: Osteoporos Int. 2007 Oct;18(10):1319-28
references.pmid: 17566815
references.citation: J Morphol. 2001 Dec;250(3):197-207
references.pmid: 11746460
references.citation: FEBS J. 2007 Sep;274(17):4428-39
references.pmid: 17680811
references.citation: Dev Cell. 2011 May 17;20(5):713-24
references.pmid: 21571227
references.citation: Bone. 2011 May 1;48(5):1186-93
references.pmid: 21334472
references.citation: Genome Biol. 2002 Jun 18;3(7):RESEARCH0034
references.pmid: 12184808
references.citation: Endocrinology. 1999 Oct;140(10):4382-9
references.pmid: 10499489
references.citation: Fish Physiol Biochem. 1994 Nov;13(5):379-86
references.pmid: 24197074
references.citation: J Biol Chem. 2003 Apr 4;278(14):11843-8
references.pmid: 12517753
references.citation: Trends Mol Med. 2012 Jun;18(6):348-59
references.pmid: 22578718
references.citation: Life Sci. 2005 Apr 22;76(23):2699-709
references.pmid: 15792836
references.citation: Expert Opin Drug Discov. 2010 Dec;5(12):1163-74
references.pmid: 22822719
references.citation: J Clin Invest. 1998 Jul 15;102(2):274-82
references.pmid: 9664068
references.citation: Bone. 1995 Aug;17(2 Suppl):77S-83S
references.pmid: 8579903
references.citation: Biol Rev Camb Philos Soc. 2009 May;84(2):315-46
references.pmid: 19382934
references.citation: Comp Biochem Physiol B. 1991;99(2):473-6
references.pmid: 1764927
references.citation: Arthritis Rheum. 2009 May;60(5):1427-37
references.pmid: 19404943
references.citation: Lab Anim. 2011 Jan;45(1):14-24
references.pmid: 21156759
references.citation: J Musculoskelet Neuronal Interact. 2010 Sep;10(3):231-6
references.pmid: 20811147
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):12748-53
references.pmid: 18753619
references.citation: Biotechnol J. 2006 Jun;1(6):651-5
references.pmid: 16892313
references.citation: N Engl J Med. 2011 Jul 7;365(1):62-70
references.pmid: 21732837
references.citation: Life Sci. 2003 Sep 12;73(17):2237-47
references.pmid: 12927593
references.citation: Cell Tissue Res. 2012 Oct;350(1):69-75
references.pmid: 22669163
references.citation: Ther Clin Risk Manag. 2009 Apr;5(2):305-10
references.pmid: 19536312
references.citation: Osteoporos Int. 2011 Jun;22(6):2007-10
references.pmid: 21523399