PMID- 29138868
OWN - NLM
STAT- MEDLINE
DCOM- 20180716
LR  - 20211204
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 17
IP  - 1
DP  - 2018 Jan
TI  - HDAC inhibitor LMK‑235 promotes the odontoblast differentiation of dental pulp 
      cells.
PG  - 1445-1452
LID - 10.3892/mmr.2017.8055 [doi]
AB  - The role of dental pulp cells (DPCs) in hard dental tissue regeneration had 
      received increasing attention because DPCs can differentiate into odontoblasts 
      and other tissue‑specific cells. In recent years, epigenetic modifications had 
      been identified to serve an important role in cell differentiation, and histone 
      deacetylase (HDAC) inhibitors have been widely studied by many researchers. 
      However, the effects of HDAC4 and HDAC5 on the differentiation of DPCs and the 
      precise molecular mechanisms remain unclear. The present study demonstrated that 
      LMK‑235, a specific human HDAC4 and HDAC5 inhibitor, increased the expression of 
      specific odontoblastic gene expression levels detected by reverse 
      transcription‑quantitative polymerase chain reaction (RT‑qPCR) in dental pulp 
      cells, and did not reduce cell proliferation tested by MTT assay after 3 days in 
      culture at a low concentration. In addition, the mRNA and protein expression 
      levels of dentin sialophosphoprotein, runt‑related transcription factor 2, 
      alkaline phosphatase (ALP) and osteocalcin were evaluated by RT‑qPCR and western 
      blotting, respectively. The increased gene and protein expression of specific 
      markers demonstrated, indicating that LMK‑235 promoted the odontoblast induction 
      of DPCs. ALP activity and mineralised nodule formation were also enhanced due to 
      the effect of LMK‑235, detected by an ALP activity test and Alizarin Red S 
      staining, respectively. Additionally, the vascular endothelial growth factor 
      (VEGF)/RAC‑gamma serine/threonine‑protein kinase (AKT)/mechanistic target of 
      rapamycin (mTOR) signalling pathway was tested to see if it takes part in the 
      differentiation of DPCs treated with LMK‑235, and it was demonstrated that the 
      mRNA expression levels of VEGF, AKT and mTOR were upregulated. These findings 
      indicated that LMK‑235 may serve a key role in the proliferation and odontoblast 
      differentiation of DPCs, and could be used to accelerate dental tissue 
      regeneration.
FAU - Liu, Zhao
AU  - Liu Z
AD  - Department of Stomatology, Nanfang Hospital, Southern Medical University, 
      Guangzhou, Guangdong 510515, P.R. China.
FAU - Chen, Ting
AU  - Chen T
AD  - Department of Stomatology, Nanfang Hospital, Southern Medical University, 
      Guangzhou, Guangdong 510515, P.R. China.
FAU - Han, Qianqian
AU  - Han Q
AD  - Department of Periodontics, Stomatology Hospital of Guangdong Province, 
      Guangzhou, Guangdong 510260, P.R. China.
FAU - Chen, Ming
AU  - Chen M
AD  - Department of Stomatology, Nanfang Hospital, Southern Medical University, 
      Guangzhou, Guangdong 510515, P.R. China.
FAU - You, Jie
AU  - You J
AD  - Department of Stomatology, Nanfang Hospital, Southern Medical University, 
      Guangzhou, Guangdong 510515, P.R. China.
FAU - Fang, Fuchun
AU  - Fang F
AD  - Department of Stomatology, Nanfang Hospital, Southern Medical University, 
      Guangzhou, Guangdong 510515, P.R. China.
FAU - Peng, Ling
AU  - Peng L
AD  - Department of Stomatology, Nanfang Hospital, Southern Medical University, 
      Guangzhou, Guangdong 510515, P.R. China.
FAU - Wu, Buling
AU  - Wu B
AD  - Department of Stomatology, Nanfang Hospital, Southern Medical University, 
      Guangzhou, Guangdong 510515, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20171114
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Cell Differentiation/*drug effects
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Dental Pulp/cytology
MH  - Gene Expression
MH  - Histone Deacetylase Inhibitors/*pharmacology
MH  - Humans
MH  - Odontoblasts/drug effects/*physiology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Vascular Endothelial Growth Factor A/metabolism
PMC - PMC5780081
EDAT- 2017/11/16 06:00
MHDA- 2018/07/17 06:00
PMCR- 2017/11/14
CRDT- 2017/11/16 06:00
PHST- 2017/01/06 00:00 [received]
PHST- 2017/08/18 00:00 [accepted]
PHST- 2017/11/16 06:00 [pubmed]
PHST- 2018/07/17 06:00 [medline]
PHST- 2017/11/16 06:00 [entrez]
PHST- 2017/11/14 00:00 [pmc-release]
AID - mmr-17-01-1445 [pii]
AID - 10.3892/mmr.2017.8055 [doi]
PST - ppublish
SO  - Mol Med Rep. 2018 Jan;17(1):1445-1452. doi: 10.3892/mmr.2017.8055. Epub 2017 Nov 
      14.