PMID- 33277707
OWN - NLM
STAT- MEDLINE
DCOM- 20210421
LR  - 20210421
IS  - 1365-2591 (Electronic)
IS  - 0143-2885 (Linking)
VI  - 54
IP  - 5
DP  - 2021 May
TI  - Mineral trioxide aggregate-induced AMPK activation stimulates odontoblastic 
      differentiation of human dental pulp cells.
PG  - 753-767
LID - 10.1111/iej.13460 [doi]
AB  - AIM: To investigate the role of autophagy in MTA-induced odontoblastic 
      differentiation of human dental pulp cells (HDPCs). METHODOLOGY: In MTA-treated 
      HDPCs, odontoblastic differentiation was assessed based on expression levels of 
      dentine sialophosphoprotein (DSPP) and dentine matrix protein 1 (DMP1), alkaline 
      phosphatase activity (ALP) activity by ALP staining and the formation of 
      mineralized nodule by Alizarin red S staining. Expression of 
      microtubule-associated protein 1A/1B-light chain3 (LC3), adenosine 
      monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin 
      (mTOR) signalling molecules and autophagy-related genes was analysed by Western 
      blot analysis and Acridine orange staining was used to detect autophagic 
      lysosome. For in vivo experiments, tooth cavity preparation models on rat molars 
      were established and the expression of proteins-related odontogenesis and 
      autophagy markers was observed by Immunohistochemistry and Western blot analysis. 
      Kruskal-Wallis with Dunn's multiple comparison was used for statistical analysis. 
      RESULTS: Mineral trioxide aggregate (MTA) promoted odontoblastic differentiation 
      of HDPCs, accompanied by autophagy induction, including formation of autophagic 
      lysosome and cleavage of LC3 to LC3II (P < 0.05). Conversely, inhibition of 
      autophagy through 3MA significantly attenuated the expression level of DSPP 
      (P < 0.05) and DMP1 (P < 0.05) as well as formation of mineralized nodules 
      (P < 0.05), indicating the functional significance of autophagy in MTA-induced 
      odontoblastic differentiation. Also, MTA increased the activity of AMPK 
      (P < 0.01), whereas inhibition of AMPK by compound C downregulated DSPP 
      (P < 0.01) and DMP1 (P < 0.05), but increased the phosphorylation of mTOR 
      (P < 0.05), p70S6 (P < 0.01) and Unc-51-like kinases 1 (ULK1) (ser757) 
      (P < 0.01), explaining the involvement of AMPK pathway in MTA-induced odontoblast 
      differentiation. In vivo study, MTA treatment after tooth cavity preparation on 
      rat molars upregulated DMP-1 and DSPP as well as autophagy-related proteins LC3II 
      and p62, and enhanced the phosphorylation of AMPK. CONCLUSION: MTA induced 
      odontoblastic differentiation and mineralization by modulating autophagy with 
      AMPK activation in HDPCs. Autophagy regulation is a new insight on regenerative 
      endodontic therapy using MTA treatment.
CI  - (c) 2020 International Endodontic Journal. Published by John Wiley & Sons Ltd.
FAU - Kim, Yoon-Jung
AU  - Kim YJ
AD  - Department of Oral Physiology, School of Dentistry, Hard Tissue Biointerface 
      Research Center, Chonnam National University, Gwangju, Korea.
FAU - Kim, Won-Jae
AU  - Kim WJ
AD  - Department of Oral Physiology, School of Dentistry, Hard Tissue Biointerface 
      Research Center, Chonnam National University, Gwangju, Korea.
FAU - Bae, Sun-Woong
AU  - Bae SW
AD  - Department of Oral Physiology, School of Dentistry, Hard Tissue Biointerface 
      Research Center, Chonnam National University, Gwangju, Korea.
FAU - Yang, Sun-Mi
AU  - Yang SM
AD  - Department of Pediatric Dentistry, School of Dentistry, Dental Science Research 
      Institute, Chonnam National University, Gwangju, Korea.
FAU - Park, Sam-Young
AU  - Park SY
AD  - Department of Oral Physiology, School of Dentistry, Hard Tissue Biointerface 
      Research Center, Chonnam National University, Gwangju, Korea.
FAU - Kim, Seon-Mi
AU  - Kim SM
AD  - Department of Pediatric Dentistry, School of Dentistry, Dental Science Research 
      Institute, Chonnam National University, Gwangju, Korea.
FAU - Jung, Ji-Yeon
AU  - Jung JY
AUID- ORCID: 0000-0002-4419-8077
AD  - Department of Oral Physiology, School of Dentistry, Hard Tissue Biointerface 
      Research Center, Chonnam National University, Gwangju, Korea.
LA  - eng
GR  - 2018-3404/Chonnam National University/
GR  - 2019R1A5A2027521/National Research Foundation of Korea (NRF) grant funded by the 
      Korea government (MSIT)/
GR  - CRI18032-1/Chonnam National University Hospital Biomedical Research Institute/
PT  - Journal Article
DEP - 20201231
PL  - England
TA  - Int Endod J
JT  - International endodontic journal
JID - 8004996
RN  - 0 (Aluminum Compounds)
RN  - 0 (Calcium Compounds)
RN  - 0 (Drug Combinations)
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (Oxides)
RN  - 0 (Phosphoproteins)
RN  - 0 (Silicates)
RN  - 0 (mineral trioxide aggregate)
RN  - EC 3.1.3.1 (Alkaline Phosphatase)
MH  - Alkaline Phosphatase
MH  - Aluminum Compounds
MH  - Animals
MH  - Calcium Compounds
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - *Dental Pulp
MH  - Drug Combinations
MH  - Extracellular Matrix Proteins
MH  - Humans
MH  - *Odontoblasts
MH  - Oxides
MH  - Phosphoproteins
MH  - Rats
MH  - Silicates
OTO - NOTNLM
OT  - autophagy
OT  - human dental pulp cells
OT  - mineral trioxide aggregate
OT  - odontoblastic differentiation
EDAT- 2020/12/06 06:00
MHDA- 2021/04/22 06:00
CRDT- 2020/12/05 05:33
PHST- 2020/11/27 00:00 [revised]
PHST- 2020/03/27 00:00 [received]
PHST- 2020/12/01 00:00 [accepted]
PHST- 2020/12/06 06:00 [pubmed]
PHST- 2021/04/22 06:00 [medline]
PHST- 2020/12/05 05:33 [entrez]
AID - 10.1111/iej.13460 [doi]
PST - ppublish
SO  - Int Endod J. 2021 May;54(5):753-767. doi: 10.1111/iej.13460. Epub 2020 Dec 31.