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

International Journal of Oral Biology 2020³â 45±Ç 4È£ p.190 ~ 196
ÀÌÀǼ±, Aryal Yam Prasad, ±èÅ¿µ, Æ÷Ä«·¼ ¿¤¸®³ª, ±èÇϸ², ¼º½ÃÁø, ¼Õ¿øÁÖ, ÀÌ¿µ±Õ, ¾ÈâÇö, ±èÀ翵,
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ÀÌÀǼ± ( Lee Eui-Seon ) - Kyungpook National University School of Dentistry Department of Biochemistry
 ( Aryal Yam Prasad ) - Kyungpook National University School of Dentistry Department of Biochemistry
±èÅ¿µ ( Kim Tae-Young ) - Kyungpook National University School of Dentistry Department of Biochemistry
Æ÷Ä«·¼ ¿¤¸®³ª ( Pokharel Elina ) - Kyungpook National University School of Dentistry Department of Biochemistry
±èÇϸ² ( Kim Ha-Rim ) - Kyungpook National University School of Dentistry Department of Biochemistry
¼º½ÃÁø ( Sung Shi-Jin ) - Kyungpook National University School of Dentistry Department of Biochemistry
¼Õ¿øÁÖ ( Sohn Wern-Joo ) - Daegu Haany University Pre-Major of Cosmetics and Pharmaceutics
ÀÌ¿µ±Õ ( Lee Young-Kyun ) - Kyungpook National University School of Dentistry Department of Biochemistry
¾ÈâÇö ( An Chang-Hyeon ) - Kyungpook National University School of Dentistry Department of Oral and Maxillofacial Radiology
±èÀ翵 ( Kim Jae-Young ) - Kyungpook National University School of Dentistry Department of Biochemistry

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.

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Apoptosis; Differentiation; Morphogenesis; Endoplasmic reticulum stress; Dentinogenesis

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