Display options
Share it on

Pharmaceuticals (Basel). 2021 Jun 03;14(6). doi: 10.3390/ph14060536.

Evaluation of Dexamethasone-Induced Osteoporosis In Vivo Using Zebrafish Scales.

Pharmaceuticals (Basel, Switzerland)

Siripat Chaichit, Takuto Sato, Huiqing Yu, Yu-Ki Tanaka, Yasumitsu Ogra, Takamasa Mizoguchi, Motoyuki Itoh

Affiliations

  1. Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
  2. Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand.

PMID: 34205111 PMCID: PMC8228068 DOI: 10.3390/ph14060536

Abstract

Glucocorticoid-induced osteoporosis (GIOP) is a major cause of secondary osteoporosis, and the pathogenic mechanisms of GIOP remain to be elucidated. Here, we show a rapid dexamethasone-induced osteoporosis animal model using zebrafish scales. Intraperitoneal injection of dexamethasone over a 5-day period suppressed the regeneration of scales. Furthermore, the circularity of the newly formed regenerated scales was also slightly reduced compared to that of the control group on day 5. The changes in bone-related enzymes, such as cathepsin K, tartrate-resistant acid phosphatase (TRAP) for bone resorption, and alkaline phosphatase (ALP) for bone formation, provide insight into the progression of bone diseases; therefore, we further developed a method to measure the activities of cathepsin K, TRAP, and ALP using zebrafish scales. We found that a lysis buffer with detergent at neutral pH under sonication efficiently helped extract these three enzymes with high activity levels. Interestingly, treatment with a dexamethasone injection produced considerably higher levels of cathepsin K activity and a lower Ca/P ratio than those in the control group, suggesting that dexamethasone increased osteoclast activity, with no significant changes in the activities of TRAP and ALP. Our GIOP model and enzyme assay method could help to design better treatments for GIOP.

Keywords: alkaline phosphatase; cathepsin K; glucocorticoid-induced osteoporosis; scale; tartrate-resistant acid phosphatase; zebrafish

References

  1. J Nippon Med Sch. 2010 Feb;77(1):4-12 - PubMed
  2. J Biol Chem. 1996 May 24;271(21):12517-24 - PubMed
  3. Mol Pharmacol. 2008 Jan;73(1):147-56 - PubMed
  4. Trends Endocrinol Metab. 2014 Apr;25(4):197-211 - PubMed
  5. Calcif Tissue Int. 2000 Sep;67(3):230-40 - PubMed
  6. Mol Cell Endocrinol. 2011 Mar 15;335(1):2-13 - PubMed
  7. Int J Exp Pathol. 2015 Feb;96(1):11-20 - PubMed
  8. Osteoporos Int. 2000;11 Suppl 6:S2-17 - PubMed
  9. Bone. 2011 Apr 1;48(4):704-12 - PubMed
  10. Front Immunol. 2012 Oct 12;3:314 - PubMed
  11. Pediatr Res. 2008 Nov;64(5):470-6 - PubMed
  12. Nucleic Acids Res. 2016 Nov 16;44(20):9611-9623 - PubMed
  13. J Pharmacol Sci. 2020 Jun;143(2):117-121 - PubMed
  14. J Biol Chem. 1994 May 27;269(21):14853-6 - PubMed
  15. Bone. 2012 Jun;50(6):1240-9 - PubMed
  16. Biochem Pharmacol. 1999 Jul 15;58(2):363-8 - PubMed
  17. BMC Mol Cell Biol. 2020 Mar 18;21(1):15 - PubMed
  18. Life Sci. 2009 Mar 27;84(13-14):482-8 - PubMed
  19. Am J Respir Crit Care Med. 2002 Sep 1;166(5):691-5 - PubMed
  20. J Biomed Sci. 2016 Jan 28;23:19 - PubMed
  21. Curr Opin Endocrinol Diabetes Obes. 2017 Dec;24(6):411-417 - PubMed
  22. J Anat. 1997 May;190 ( Pt 4):545-61 - PubMed
  23. Injury. 2016 Jun;47 Suppl 2:S11-20 - PubMed
  24. Development. 2019 Sep 20;146(18): - PubMed
  25. Bonekey Rep. 2014 Sep 10;3:570 - PubMed
  26. J Fish Dis. 1998 Jan;21(1):29-38 - PubMed
  27. Bone. 2015 May;74:106-13 - PubMed
  28. Biochemistry. 2000 Jan 25;39(3):529-36 - PubMed
  29. Nat Rev Genet. 2007 May;8(5):353-67 - PubMed
  30. Clin Cases Miner Bone Metab. 2009 May;6(2):114-6 - PubMed
  31. Biomark Res. 2017 May 18;5:18 - PubMed
  32. J Bone Miner Res. 2000 Jul;15(7):1337-45 - PubMed
  33. Osteoporos Int. 2014 Feb;25(2):567-78 - PubMed
  34. Am J Pathol. 2001 Dec;159(6):2167-77 - PubMed
  35. RMD Open. 2015 Apr 08;1(1):e000014 - PubMed
  36. Rheumatology (Oxford). 2013 Aug;52(8):1529-33 - PubMed
  37. Dis Model Mech. 2014 Feb;7(2):181-92 - PubMed
  38. Annu Rev Pathol. 2011;6:121-45 - PubMed
  39. Bonekey Rep. 2012 Jul 1;1: - PubMed
  40. Int J Dev Biol. 2004;48(2-3):233-47 - PubMed
  41. Clin Pharmacol Ther. 2008 Jan;83(1):172-6 - PubMed
  42. Front Endocrinol (Lausanne). 2019 Jan 29;10:6 - PubMed
  43. J Mol Histol. 2012 Oct;43(5):589-95 - PubMed
  44. PLoS One. 2014 Feb 19;9(2):e89347 - PubMed
  45. Dis Model Mech. 2014 Jul;7(7):739-43 - PubMed
  46. J Bone Miner Res. 1999 Oct;14(10):1654-63 - PubMed
  47. Biomed Res Int. 2019 Jan 22;2019:5859641 - PubMed
  48. Mol Pathol. 2002 Apr;55(2):65-72 - PubMed
  49. Tissue Cell. 1989;21(3):447-62 - PubMed
  50. Endocrine. 2018 Jul;61(1):7-16 - PubMed
  51. PLoS One. 2011;6(7):e22608 - PubMed
  52. Am Fam Physician. 1998 Aug;58(2):443-50 - PubMed
  53. Nat Methods. 2012 Jul;9(7):671-5 - PubMed
  54. Nature. 2013 Apr 25;496(7446):498-503 - PubMed
  55. Bone Res. 2018 Jun 14;6:19 - PubMed
  56. Expert Opin Investig Drugs. 2009 May;18(5):585-600 - PubMed
  57. J Pathol. 2001 Oct;195(3):375-82 - PubMed

Publication Types

Grant support