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Autophagy-Related Protein MAP1LC3C Plays a Crucial Role in Odontogenic Differentiation of Human Dental Pulp Cells

Tissue Engineering and Regenerative Medicine 2021년 18권 2호 p.265 ~ 277
조희승, 박삼영, 김선미, 김원재, 정지연,
소속 상세정보
조희승 ( Cho Heui-Seung ) - Chonnam National University School of Dentistry Department of Oral Physiology
박삼영 ( Park Sam-Young ) - Chonnam National University School of Dentistry Department of Oral Physiology
김선미 ( Kim Sun-Mi ) - Chonnam National University School of Dentistry Department of Pediatric Dentistry
김원재 ( Kim Won-Jae ) - Chonnam National University School of Dentistry Department of Oral Physiology
정지연 ( Jung Ji-Yeon ) - Chonnam National University School of Dentistry Department of Oral Physiology

Abstract


Background: Autophagy plays important roles in odontogenic differentiation of dental pulp cells (DPCs) in the developmental stage of tooth bud. Few studies have reported the role of autophagy during reparative dentin formation process. The objective of this study was to discover gene expression pattern correlated to autophagy and their role during odontogenic differentiation process in DPCs.

Methods: After tooth cavities were prepared on the mesial surface of lower first molar crown of rats. Odontogenic differentiation and reparative dentin formation were assessed based on detection of morphology change with hematoxylin and eosin staining.

Results: After tooth cavities were prepared on the mesial surface of lower first molar crown of rats, odontogenic differentiation and reparative dentin formation were assessed based on detection of morphology change with hematoxylin and eosin staining and dentin sialophosphoprotein (DSPP), whereas autophagy inhibitor 3-methyladenine (3MA) reversed. Results of quantitative polymerized chain reaction array of autophagosome formation related genes revealed that GABARAPL2 was prominently upregulated while expression of other ATG8 family members were moderately increased after tooth cavity preparation. In addition, human DPCs incubated in differentiation medium predominantly upregulated MAP1LC3C, which selectively decreased by 3MA but not by autophagy enhancer trehalose. Knock-down of MAP1LC3C using shRNA resulted in strong downregulation of dentin matrix protein 1 and DSPP as well-known odontogenic marker compared to knock-down of MAP1LC3B during odontogenic differentiation process of human DPCs.

Conclusion: Our results suggest that MAP1LC3C plays a crucial role in odontogenic differentiation of human DPCs via regulating autophagic flux.

키워드

Cell differentiation; Odontogenesis; Pulp biology; Stem cells

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