Alteration of cellular events in tooth development by chemical chaperon, TUDCA treatment
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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.
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.
참고문헌 (36)
- Markku Larmas, "Odontoblast Function Seen as the Response of Dentinal Tissue to Dental Caries", Advances in Dental Research, 15(1), pp.68~71 (2001), SAGE Publications[DOI]
- Nobuyuki Kawashima, "Odontoblasts: Specialized hard-tissue-forming cells in the dentin-pulp complex", Congenital Anomalies, 56(4), pp.144~153 (2016), Wiley[DOI]
- Thimios Mitsiadis, "Odontoblasts in the dental pulp immune response", Journal of Experimental Zoology Part B: Molecular and Developmental Evolution, 312B(5), pp.425~436 (2009), Wiley[DOI]
- I Thesleff, "Molecular regulation of tooth development", Bone, 25(1), pp.123~125 (1999), Elsevier BV[DOI]
- Nanci A, "Ten Cate’s oral histology: development, structure, and function" (2017), Elsevier
- D.H. Pashley, "Dynamics of the Pulpo-Dentin Complex", Critical Reviews in Oral Biology & Medicine, 7(2), pp.104~133 (1996), SAGE Publications[DOI]
- Anders Linde, "Dentinogenesis", Critical Reviews in Oral Biology & Medicine, 4(5), pp.679~728 (1993), SAGE Publications[DOI]
- Michel Goldberg, "A comparative study of the transition between predentin and dentin, using various preparative procedures in the rat", European Journal of Oral Sciences, 104(3), pp.269~277 (1996), Wiley[DOI]
- Michel Goldberg, "Dentin structure composition and mineralization", Frontiers in Bioscience, E3(2), pp.711~735 (2011), Bioscience Research Institute Pte. Ltd[DOI]
- Smith AJ, "Reactionary dentinogenesis", Int J Dev Biol, 39, pp.273~280 (1995)
- S. Simon, "Regenerative endodontics", British Dental Journal, 216(6), pp.E13~E13 (2014), Springer Science and Business Media LLC[DOI]
- Rebecca Babb, "Axin2-expressing cells differentiate into reparative odontoblasts via autocrine Wnt", β-catenin signaling in response to tooth damage, 2017, pp.7(1), ~[DOI]
- Miao Wang, "Protein misfolding in the endoplasmic reticulum as a conduit to human disease", Nature, 529(7586), pp.326~335 (2016), Springer Science and Business Media LLC[DOI]
- Tiziana Anelli, "Protein quality control in the early secretory pathway", The EMBO Journal, 27(2), pp.315~327 (2008), Wiley[DOI]
- David Ron, "Signal integration in the endoplasmic reticulum unfolded protein response", Nature Reviews Molecular Cell Biology, 8(7), pp.519~529 (2007), Springer Science and Business Media LLC[DOI]
- Shiyu Wang, "The impact of the unfolded protein response on human disease", Journal of Cell Biology, 197(7), pp.857~867 (2012), Rockefeller University Press[DOI]
- Ira Tabas, "Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress", Nature Cell Biology, 13(3), pp.184~190 (2011), Springer Science and Business Media LLC[DOI]
- Yanjun Ma, "ER chaperone functions during normal and stress conditions", Journal of Chemical Neuroanatomy, 28(1-2), pp.51~65 (2004), Elsevier BV[DOI]
- Huifang M. Zhang, "Coxsackievirus B3 Infection Activates the Unfolded Protein Response and Induces Apoptosis through Downregulation of p58IPK and Activation of CHOP and SREBP1", Journal of Virology, 84(17), pp.8446~8459 (2010), American Society for Microbiology[DOI]
- Scott A. Oakes, "The Role of Endoplasmic Reticulum Stress in Human Pathology", Annual Review of Pathology: Mechanisms of Disease, 10(1), pp.173~194 (2015), Annual Reviews[DOI]
- Yam Prasad Aryal, "An endoplasmic reticulum stress regulator, Tmbim6, modulates secretory stage of mice molar", Journal of Cellular Physiology, 234(11), pp.20354~20365 (2019), Wiley[DOI]
- Steven J. Brookes, "The Unfolded Protein Response in Amelogenesis and Enamel Pathologies", Frontiers in Physiology, 8, pp.653~ (2017), Frontiers Media SA[DOI]
- Brookes SJ, "Endoplasmic reticulum stress in amelogenesis imperfecta and phenotypic rescue using 4-phenylbutyrate", Hum Mol Genet, 23, pp.2468~2480 (2014)[DOI]
- Omar Mohammed Amen, "Endoplasmic Reticulum Stress Activates Unfolded Protein Response Signaling and Mediates Inflammation, Obesity, and Cardiac Dysfunction: Therapeutic and Molecular Approach", Frontiers in Pharmacology, 10, pp.977~ (2019), Frontiers Media SA[DOI]
- Konstantinos N Lazaridis, "Ursodeoxycholic acid ‘mechanisms of action and clinical use in hepatobiliary disorders’", Journal of Hepatology, 35(1), pp.134~146 (2001), Elsevier BV[DOI]
- Jagadeesh Kumar Uppala, "Chemical chaperone, TUDCA unlike PBA, mitigates protein aggregation efficiently and resists ER and non-ER stress induced HepG2 cell death", Scientific Reports, 7(1), pp.3831~ (2017), Springer Science and Business Media LLC[DOI]
- Gustav Paumgartner, "Mechanisms of action and therapeutic efficacy of ursodeoxycholic acid in cholestatic liver disease", Clinics in Liver Disease, 8(1), pp.67~81 (2004), Elsevier BV[DOI]
- Yeon Yi Lee, "Tauroursodeoxycholate (TUDCA), chemical chaperone, enhances function of islets by reducing ER stress", Biochemical and Biophysical Research Communications, 397(4), pp.735~739 (2010), Elsevier BV[DOI]
- Jae-Young Kim, "Shh and ROCK1 modulate the dynamic epithelial morphogenesis in circumvallate papilla development", Developmental Biology, 325(1), pp.273~280 (2009), Elsevier BV[DOI]
- Sanjiv Neupane, "Signaling Modulations of miR-206-3p in Tooth Morphogenesis", International Journal of Molecular Sciences, 21(15), pp.5251~ (2020), MDPI AG[DOI]
- Sanjiv Neupane, "Developmental regulations of Perp in mice molar morphogenesis", Cell and Tissue Research, 358(1), pp.109~121 (2014), Springer Science and Business Media LLC[DOI]
- W.-J. Sohn, "Contribution of Mesenchymal Proliferation in Tooth Root Morphogenesis", Journal of Dental Research, 93(1), pp.78~83 (2014), SAGE Publications[DOI]
- Amy S. Lee, "The ER chaperone and signaling regulator GRP78", BiP as a monitor of endoplasmic reticulum stress, 2005, pp.35(4), 373~381[DOI]
- Tijun Wu, "HRD1, an Important Player in Pancreatic β-Cell Failure and Therapeutic Target for Type 2 Diabetic Mice", Diabetes, 69(5), pp.940~953 (2020), American Diabetes Association[DOI]
- Claudio Hetz, "The unfolded protein response: controlling cell fate decisions under ER stress and beyond", Nature Reviews Molecular Cell Biology, 13(2), pp.89~102 (2012), Springer Science and Business Media LLC[DOI]
- Shengyi Sun, "IRE1α is an endogenous substrate of endoplasmic-reticulum-associated degradation", Nature Cell Biology, 17(12), pp.1546~1555 (2015), Springer Science and Business Media LLC[DOI]