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Effect of remifentanil on pre-osteoclast cell differentiation in vitro

  • Jeon, Hyun-Ook (Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Pusan National University, Dental Research Institute) ;
  • Choi, In-Seok (Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Pusan National University, Dental Research Institute) ;
  • Yoon, Ji-Young (Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Pusan National University, Dental Research Institute) ;
  • Kim, Eun-Jung (Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Pusan National University, Dental Research Institute) ;
  • Yoon, Ji-Uk (Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University) ;
  • Cho, Ah-Reum (Department of Anesthesia and Pain Medicine, Pusan National University Hospital) ;
  • Kim, Hyung-Joon (Department of Oral Physiology, School of Dentistry, Pusan National University) ;
  • Kim, Cheul-Hong (Department of Dental Anesthesia and Pain Medicine, School of Dentistry, Pusan National University, Dental Research Institute)
  • Received : 2018.01.14
  • Accepted : 2018.01.25
  • Published : 2018.02.28

Abstract

Background: The structure and function of bone tissue is maintained through a constant remodeling process, which is maintained by the balance between osteoblasts and osteoclasts. The failure of bone remodeling can lead to pathological conditions of bone structure and function. Remifentanil is currently used as a narcotic analgesic agent in general anesthesia and sedation. However, the effect of remifentanil on osteoclasts has not been studied. Therefore, we investigated the effect of remifentanil on pre-osteoclast (pre-OCs) differentiation and the mechanism of osteoclast differentiation in the absence of specific stimulus. Methods: Pre-OCs were obtained by culturing bone marrow-derived macrophages (BMMs) in osteoclastogenic medium for 2 days and then treated with various concentration of remifentanil. The mRNA expression of NFATc1 and c-fos was examined by using real-time PCR. We also examined the effect of remifentanil on the osteoclast-specific genes TRAP, cathepsin K, calcitonin receptor, and DC-STAMP. Finally, we examined the influence of remifentanil on the migration of pre-OCs by using the Boyden chamber assay. Results: Remifentanil increased pre-OC differentiation and osteoclast size, but did not affect the mRNA expression of NFATc1 and c-fos or significantly affect the expression of TRAP, cathepsin K, calcitonin receptor, and DC-STAMP. However, remifentanil increased the migration of pre-OCs. Conclusions: This study suggested that remifentanil promotes the differentiation of pre-OCs and induces maturation, such as increasing osteoclast size. In addition, the increase in osteoclast size was mediated by the enhancement of pre-OC migration and cell fusion.

Keywords

References

  1. Chambers TJ. Regulation of the differentiation and function of osteoclasts. J Pathol 2000; 192: 4-13. https://doi.org/10.1002/1096-9896(2000)9999:9999<::AID-PATH645>3.0.CO;2-Q
  2. Hauge EM, Qvesel D, Eriksen EF, Mosekilde L, Melsen F. Cancellous bone remodeling occurs in specialized compartments lined by cells expressing osteoblastic markers. J Bone Miner Res 2001; 16: 1575-82. https://doi.org/10.1359/jbmr.2001.16.9.1575
  3. Raggatt LJ, Partridge NC. Cellular and molecular mechanisms of bone remodeling. J Biol Chem 2010; 285: 25103-8. https://doi.org/10.1074/jbc.R109.041087
  4. Hadjidakis DJ, Androulakis II. Bone remodeling. Ann N Y Acad Sci 2006; 1092: 385-96. https://doi.org/10.1196/annals.1365.035
  5. Teitelbaum SL. Bone resorption by osteoclasts. Science 2000; 289: 1504-8. https://doi.org/10.1126/science.289.5484.1504
  6. Roodman GD. Advances in bone biology: The osteoclast. Endocr Rev 1996; 17: 308-32.
  7. Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 1998; 93: 165-76. https://doi.org/10.1016/S0092-8674(00)81569-X
  8. Chen EH, Grote E, Mohler W, Vignery A. Cell-cell fusion. FEBS Lett 2007; 581: 2181-93. https://doi.org/10.1016/j.febslet.2007.03.033
  9. Teitelbaum SL, Ross FP. Genetic regulation of osteoclast development and function. Nat Rev Genet 2003; 4: 638-49. https://doi.org/10.1038/nrg1122
  10. Vignery A. Macrophage fusion: the making of osteoclasts and giant cells. J Exp Med 2005; 202: 337-40. https://doi.org/10.1084/jem.20051123
  11. Vignery A. Osteoclasts and giant cells: macrophagemacrophage fusion mechanism. Int J Exp Pathol 2000; 81: 291-304. https://doi.org/10.1046/j.1365-2613.2000.00164.x
  12. Glass PS, Gan TJ, Howell S. a review of the pharmacokinetics and pharmacodynamics of remifentanil. Anesth Analg 1999; 89: S7-14.
  13. Scott LJ, Perry CM. Remifentanil: A review of its use during the induction and maintenance of general anaesthesia. Drugs 2005; 65: 1793-823. https://doi.org/10.2165/00003495-200565130-00007
  14. Yoon JY, Kim DW, Kim EJ, Park BS, Yoon JU, Kim HJ, et al. Protective effects of remifentanil against $H_2O_2$-induced oxidative stress in human osteoblasts. J Dent Anesth Pain Med 2016; 16: 263-71. https://doi.org/10.17245/jdapm.2016.16.4.263
  15. Baik SW, Park BS, Kim YH, Kim YD, Kim CH, Yoon JY, et al. Effects of remifentanil preconditioning on osteoblasts under hypoxia-reoxygenation condition. Int J Med Sci 2015; 12: 583-9. https://doi.org/10.7150/ijms.11839
  16. Ha J, Choi HS, Lee Y, Lee ZH, Kim HH. Caffeic acid phenethyl ester inhibits osteoclastogenesis by suppressing NF kappaB and downregulating NFATc1 and c-Fos. Int Immunopharmacol 2009; 9: 774-80. https://doi.org/10.1016/j.intimp.2009.03.001
  17. Rao A, Luo C, Hogan PG. Transcription factors of the NFAT family: regulation and function. Annu Rev Immunol 1997; 15: 707-47. https://doi.org/10.1146/annurev.immunol.15.1.707
  18. Takayanagi H, Kim S, Koga T, Nishina H, Isshiki M, Yoshida H, et al. Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev Cell 2002; 3: 889-901. https://doi.org/10.1016/S1534-5807(02)00369-6
  19. Takayanagi H. Mechanistic insight into osteoclast differentiation in osteoimmunology. J Mol Med (Berl) 2005; 83: 170-9. https://doi.org/10.1007/s00109-004-0612-6
  20. Yagi M, Ninomiya K, Fujita N, Suzuki T, Iwasaki R, Morita K, et al. Induction of DC-STAMP by alternative activation and downstream signaling mechanisms. J Bone Miner Res 2007; 22: 992-1001. https://doi.org/10.1359/jbmr.070401
  21. Felix R, Hofstetter W, Wetterwald A, Cecchini MG, Fleisch H. Role of colony-stimulating factor-1 in bone metabolism. J Cell Biochem 1994; 55: 340-9. https://doi.org/10.1002/jcb.240550311
  22. Grigoriadis AE, Wang ZQ, Cecchini MG, Hofstetter W, Felix R, Fleisch HA, et al. c-Fos: A key regulator of osteoclast-macrophage lineage determination and bone remodeling. Science 1994; 266: 443-8. https://doi.org/10.1126/science.7939685
  23. Kular J, Tickner J, Chim SM, Xu J. An overview of the regulation of bone remodelling at the cellular level. Clin Biochem 2012; 45: 863-73. https://doi.org/10.1016/j.clinbiochem.2012.03.021
  24. Ishii M, Saeki Y. Osteoclast cell fusion: mechanisms and molecules. Mod Rheumatol 2008; 18: 220-7. https://doi.org/10.3109/s10165-008-0051-2
  25. Corral DA, Amling M, Priemel M, Loyer E, Fuchs S, Ducy P, et al. Dissociation between bone resorption and bone formation in osteopenic transgenic mice. Proc Natl Acad Sci U S A 1998; 95: 13835-40. https://doi.org/10.1073/pnas.95.23.13835
  26. Hou GQ, Guo C, Song GH, Fang N, Fan WJ, Chen XD, et al. Lipopolysaccharide (LPS) promotes osteoclast differentiation and activation by enhancing the MAPK pathway and COX-2 expression in RAW264.7 cells. Int J Mol Med 2013; 32: 503-10. https://doi.org/10.3892/ijmm.2013.1406
  27. Zou W, Bar-Shavit Z. Dual modulation of osteoclast differentiation by lipopolysaccharide. J Bone Miner Res 2002; 17: 1211-8. https://doi.org/10.1359/jbmr.2002.17.7.1211