International Journal of Oral Biology

The Korean Academy of Oral Biology (대한구강생물학회)
권호 표지
DOI QR코드

DOI QR Code

Alteration of cellular events in tooth development by chemical chaperon, Tauroursodeoxycholic acid treatment

  • Lee, Eui-Seon (Department of Biochemistry, School of Dentistry, Kyungpook National University) ;
  • Aryal, Yam Prasad (Department of Biochemistry, School of Dentistry, Kyungpook National University) ;
  • Kim, Tae-Young (Department of Biochemistry, School of Dentistry, Kyungpook National University) ;
  • Pokharel, Elina (Department of Biochemistry, School of Dentistry, Kyungpook National University) ;
  • Kim, Harim (Department of Biochemistry, School of Dentistry, Kyungpook National University) ;
  • Sung, Shijin (Department of Biochemistry, School of Dentistry, Kyungpook National University) ;
  • Sohn, Wern-Joo (Pre-Major of Cosmetics and Pharmaceutics, Daegu Haany University) ;
  • Lee, Youngkyun (Department of Biochemistry, School of Dentistry, Kyungpook National University) ;
  • An, Chang-Hyeon (Department of Oral and Maxillofacial Radiology, IHBR, School of Dentistry, Kyungpook National University) ;
  • Kim, Jae-Young (Department of Biochemistry, School of Dentistry, Kyungpook National University)
  • Received : 2020.11.23
  • Accepted : 2020.12.08
  • Published : 2020.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Several factors, including genetic and environmental insults, impede protein folding and secretion in the endoplasmic reticulum (ER). Accumulation of unfolded or mis-folded protein in the ER manifests as ER stress. To cope with this morbid condition of the ER, recent data has suggested that the intracellular event of an unfolded protein response plays a critical role in managing the secretory load and maintaining proteostasis in the ER. Tauroursodeoxycholic acid (TUDCA) is a chemical chaperone and hydrophilic bile acid that is known to inhibit apoptosis by attenuating ER stress. Numerous studies have revealed that TUDCA affects hepatic diseases, obesity, and inflammatory illnesses. Recently, molecular regulation of ER stress in tooth development, especially during the secretory stage, has been studied. Therefore, in this study, we examined the developmental role of ER stress regulation in tooth morphogenesis using in vitro organ cultivation methods with a chemical chaperone treatment, TUDCA. Altered cellular events including proliferation, apoptosis, and dentinogenesis were examined using immunostaining and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. In addition, altered localization patterns of the formation of hard tissue matrices related to molecules, including amelogenin and nestin, were examined to assess their morphological changes. Based on our findings, modulating the role of the chemical chaperone TUDCA in tooth morphogenesis, especially through the modulation of cellular proliferation and apoptosis, could be applied as a supporting data for tooth regeneration for future studies.

Keywords

References

  1. Larmas M. Odontoblast function seen as the response of dentinal tissue to dental caries. Adv Dent Res 2001;15:68-71. doi: 10.1177/08959374010150011701.
  2. Kawashima N, Okiji T. Odontoblasts: Specialized hard-tissue-forming cells in the dentin-pulp complex. Congenit Anom (Kyoto) 2016;56:144-53. doi: 10.1111/cga.12169.
  3. Farges JC, Keller JF, Carrouel F, Durand SH, Romeas A, Bleicher F, Lebecque S, Staquet MJ. Odontoblasts in the dental pulp immune response. J Exp Zool B Mol Dev Evol 2009;312B:425-36. doi: 10.1002/jez.b.21259.
  4. Thesleff I, Aberg T. Molecular regulation of tooth development. Bone 1999;25:123-5. doi: 10.1016/s8756-3282(99)00119-2.
  5. Nanci A. Ten Cate's oral histology: development, structure, and function. 9th ed. St. Louis: Elsevier; 2017.
  6. Pashley DH. Dynamics of the pulpo-dentin complex. Crit Rev Oral Biol Med 1996;7:104-33. doi: 10.1177/10454411960070020101.
  7. Linde A, Goldberg M. Dentinogenesis. Crit Rev Oral Biol Med 1993;4:679-728. doi: 10.1177/10454411930040050301.
  8. Goldberg M, Septier D. A comparative study of the transition between predentin and dentin, using various preparative procedures in the rat. Eur J Oral Sci 1996;104:269-77. doi: 10.1111/j.1600-0722.1996.tb00077.x.
  9. Goldberg M, Kulkarni AB, Young M, Boskey A. Dentin: structure, composition and mineralization. Front Biosci (Elite Ed) 2011;3:711-35. doi: 10.2741/e281.
  10. Smith AJ, Cassidy N, Perry H, Begue-Kirn C, Ruch JV, Lesot H. Reactionary dentinogenesis. Int J Dev Biol 1995;39:273-80.
  11. Simon S, Smith AJ. Regenerative endodontics. Br Dent J 2014;216:E13. doi: 10.1038/sj.bdj.2014.243.
  12. Babb R, Chandrasekaran D, Carvalho Moreno Neves V, Sharpe PT. Axin2-expressing cells differentiate into reparative odontoblasts via autocrine Wnt/β-catenin signaling in response to tooth damage. Sci Rep 2017;7:3102. doi: 10.1038/s41598-017-03145-6.
  13. Wang M, Kaufman RJ. Protein misfolding in the endoplasmic reticulum as a conduit to human disease. Nature 2016;529:326-35. doi: 10.1038/nature17041.
  14. Anelli T, Sitia R. Protein quality control in the early secretory pathway. EMBO J 2008;27:315-27. doi: 10.1038/sj.emboj.7601974.
  15. Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 2007;8:519-29. doi: 10.1038/nrm2199.
  16. Wang S, Kaufman RJ. The impact of the unfolded protein response on human disease. J Cell Biol 2012;197:857-67. doi: 10.1083/jcb.201110131.
  17. Tabas I, Ron D. Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat Cell Biol 2011;13:184-90. doi: 10.1038/ncb0311-184.
  18. Ma Y, Hendershot LM. ER chaperone functions during normal and stress conditions. J Chem Neuroanat 2004;28:51-65. doi: 10.1016/j.jchemneu.2003.08.007.
  19. Zhang HM, Ye X, Su Y, Yuan J, Liu Z, Stein DA, Yang D. Coxsackievirus B3 infection activates the unfolded protein response and induces apoptosis through downregulation of p58IPK and activation of CHOP and SREBP1. J Virol 2010;84:8446-59. doi: 10.1128/JVI.01416-09.
  20. Oakes SA, Papa FR. The role of endoplasmic reticulum stress in human pathology. Annu Rev Pathol 2015;10:173-94. doi: 10.1146/annurev-pathol-012513-104649.
  21. Aryal YP, Neupane S, Adhikari N, An CH, Ha JH, Kwon TY, Yamamoto H, Jung JK, Park EK, Kim JY, Cho SW, Sohn WJ, Lee Y, Chae HJ, Kim HR, Kim JY. An endoplasmic reticulum stress regulator, Tmbim6, modulates secretory stage of mice molar. J Cell Physiol 2019;234:20354-65. doi: 10.1002/jcp.28635.
  22. Brookes SJ, Barron MJ, Dixon MJ, Kirkham J. The unfolded protein response in amelogenesis and enamel pathologies. Front Physiol 2017;8:653. doi: 10.3389/fphys.2017.00653.
  23. Brookes SJ, Barron MJ, Boot-Handford R, Kirkham J, Dixon MJ. Endoplasmic reticulum stress in amelogenesis imperfecta and phenotypic rescue using 4-phenylbutyrate. Hum Mol Genet 2014;23:2468-80. doi: 10.1093/hmg/ddt642.
  24. Amen OM, Sarker SD, Ghildyal R, Arya A. Endoplasmic reticulum stress activates unfolded protein response signaling and mediates inflammation, obesity, and cardiac dysfunction: therapeutic and molecular approach. Front Pharmacol 2019;10:977. doi: 10.3389/fphar.2019.00977.
  25. Lazaridis KN, Gores GJ, Lindor KD. Ursodeoxycholic acid 'mechanisms of action and clinical use in hepatobiliary disorders'. J Hepatol 2001;35:134-46. doi: 10.1016/s0168-8278(01)00092-7.
  26. Uppala JK, Gani AR, Ramaiah KVA. Chemical chaperone, TUDCA unlike PBA, mitigates protein aggregation efficiently and resists ER and non-ER stress induced HepG2 cell death. Sci Rep 2017;7:3831. doi: 10.1038/s41598-017-03940-1.
  27. Paumgartner G, Beuers U. Mechanisms of action and therapeutic efficacy of ursodeoxycholic acid in cholestatic liver disease. Clin Liver Dis 2004;8:67-81, vi. doi: 10.1016/S1089-3261(03)00135-1.
  28. Lee YY, Hong SH, Lee YJ, Chung SS, Jung HS, Park SG, Park KS. Tauroursodeoxycholate (TUDCA), chemical chaperone, enhances function of islets by reducing ER stress. Biochem Biophys Res Commun 2010;397:735-9. doi: 10.1016/j.bbrc.2010.06.022.
  29. Kim JY, Lee MJ, Cho KW, Lee JM, Kim YJ, Kim JY, Jung HI, Cho JY, Cho SW, Jung HS. Shh and ROCK1 modulate the dynamic epithelial morphogenesis in circumvallate papilla development. Dev Biol 2009;325:273-80. doi: 10.1016/j.ydbio.2008.10.034.
  30. Neupane S, Aryal YP, Kim TY, Yeon CY, An CH, Kim JY, Yamamoto H, Lee Y, Sohn WJ, Kim JY. Signaling modulations of miR-206-3p in tooth morphogenesis. Int J Mol Sci 2020;21:5251. doi: 10.3390/ijms21155251.
  31. Neupane S, Sohn WJ, Rijal G, Lee YJ, Lee S, Yamamoto H, An CH, Cho SW, Lee Y, Shin HI, Kwon TY, Kim JY. Developmental regulations of Perp in mice molar morphogenesis. Cell Tissue Res 2014;358:109-21. doi: 10.1007/s00441-014-1908-7.
  32. Sohn WJ, Choi MA, Yamamoto H, Lee S, Lee Y, Jung JK, Jin MU, An CH, Jung HS, Suh JY, Shin HI, Kim JY. Contribution of mesenchymal proliferation in tooth root morphogenesis. J Dent Res 2014;93:78-83. doi: 10.1177/0022034513511247.
  33. Lee AS. The ER chaperone and signaling regulator GRP78/BiP as a monitor of endoplasmic reticulum stress. Methods 2005;35:373-81. doi: 10.1016/j.ymeth.2004.10.010.
  34. Wu T, Zhang S, Xu J, Zhang Y, Sun T, Shao Y, Wang J, Tang W, Chen F, Han X. HRD1, an important player in pancreatic β-cell failure and therapeutic target for type 2 diabetic mice. Diabetes 2020;69:940-53. doi: 10.2337/db19-1060.
  35. Hetz C. The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol 2012;13:89-102. doi: 10.1038/nrm3270.
  36. Sun S, Shi G, Sha H, Ji Y, Han X, Shu X, Ma H, Inoue T, Gao B, Kim H, Bu P, Guber RD, Shen X, Lee AH, Iwawaki T, Paton AW, Paton JC, Fang D, Tsai B, Yates JR 3rd, Wu H, Kersten S, Long Q, Duhamel GE, Simpson KW, Qi L. IRE1α is an endogenous substrate of endoplasmic-reticulum-associated degradation. Nat Cell Biol 2015;17:1546-55. doi: 10.1038/ncb3266.