PMID- 25019367
OWN - NLM
STAT- MEDLINE
DCOM- 20150521
LR  - 20181202
IS  - 1878-5875 (Electronic)
IS  - 1357-2725 (Linking)
VI  - 54
DP  - 2014 Sep
TI  - Histone deacetylase 8 suppresses osteogenic differentiation of bone marrow 
      stromal cells by inhibiting histone H3K9 acetylation and RUNX2 activity.
PG  - 68-77
LID - S1357-2725(14)00222-2 [pii]
LID - 10.1016/j.biocel.2014.07.003 [doi]
AB  - Bone marrow stromal cells (BMSCs) are multipotent progenitor cells with 
      capacities to differentiate into the various cell types and hold great promise in 
      regenerative medicine. The regulatory roles of histone deacetylases (HDACs) in 
      osteoblast differentiation process have been increasingly recognized; however, 
      little is known about the precise roles of HDAC8 in the osteogenic 
      differentiation of BMSCs. Herein we aimed to investigate the roles of HDAC8 in 
      the osteogenic differentiation of rat BMSCs by pharmacological and genetic 
      manipulations in vitro. During osteogenic differentiation of BMSCs, 
      pharmacological inhibition of HDAC8 by HDAC inhibitor valproic acid (VPA) 
      promoted the level of histone H3 lysine 9 acetylation (H3K9Ac) and significantly 
      enhanced the expression of osteogenesis-related genes Runx2, Osterix, osteocalcin 
      (OCN), osteopontin (OPN) and alkaline phosphatase (ALP). Similarly, knockdown of 
      HDAC8 using short interfering RNA triggered H3K9Ac and enhanced osteogenic 
      differentiation of BMSCs, largely phenocopied the effects of VPA-mediated HDAC8 
      depletion. However, enforced expression of HDAC8 significantly reduced the level 
      of H3K9Ac and inhibited osteogenic differentiation of BMSCs, which can be 
      attenuated by VPA addition. Mechanistically, HDAC8 suppressed 
      osteogenesis-related genes expression by removing the acetylation of histone 
      H3K9, thus leading to transcriptional inhibition during osteogenic 
      differentiation of BMSCs. Importantly, we found that HDAC8 physically associated 
      with Runx2 to repress its transcriptional activity and this association decreased 
      when BMSCs underwent osteogenic differentiation. Taken together, these results 
      indicate that epigenetic regulation of Runx2 by HDAC8-mediated histone H3K9 
      acetylation is required for the proper osteogenic differentiation of BMSCs.
CI  - Copyright (c) 2014 Elsevier Ltd. All rights reserved.
FAU - Fu, Yu
AU  - Fu Y
AD  - Department of Oral and Maxillofacial Surgery, School of Stomatology, Nanjing 
      Medical University, Nanjing 210029, Jiangsu Province, China; Institute of 
      Stomatology, School of Stomatology, Nanjing Medical University, Nanjing 210029, 
      Jiangsu Province, China.
FAU - Zhang, Ping
AU  - Zhang P
AD  - Department of Oral and Maxillofacial Surgery, School of Stomatology, Nanjing 
      Medical University, Nanjing 210029, Jiangsu Province, China.
FAU - Ge, Jie
AU  - Ge J
AD  - Institute of Stomatology, School of Stomatology, Nanjing Medical University, 
      Nanjing 210029, Jiangsu Province, China.
FAU - Cheng, Jie
AU  - Cheng J
AD  - Department of Oral and Maxillofacial Surgery, School of Stomatology, Nanjing 
      Medical University, Nanjing 210029, Jiangsu Province, China.
FAU - Dong, Weijie
AU  - Dong W
AD  - Department of Oral and Maxillofacial Surgery, School of Stomatology, Nanjing 
      Medical University, Nanjing 210029, Jiangsu Province, China; Institute of 
      Stomatology, School of Stomatology, Nanjing Medical University, Nanjing 210029, 
      Jiangsu Province, China.
FAU - Yuan, Hua
AU  - Yuan H
AD  - Department of Oral and Maxillofacial Surgery, School of Stomatology, Nanjing 
      Medical University, Nanjing 210029, Jiangsu Province, China.
FAU - Du, Yifei
AU  - Du Y
AD  - Department of Oral and Maxillofacial Surgery, School of Stomatology, Nanjing 
      Medical University, Nanjing 210029, Jiangsu Province, China.
FAU - Yang, Mifang
AU  - Yang M
AD  - Institute of Stomatology, School of Stomatology, Nanjing Medical University, 
      Nanjing 210029, Jiangsu Province, China.
FAU - Sun, Ruoxing
AU  - Sun R
AD  - Institute of Stomatology, School of Stomatology, Nanjing Medical University, 
      Nanjing 210029, Jiangsu Province, China.
FAU - Jiang, Hongbing
AU  - Jiang H
AD  - Department of Oral and Maxillofacial Surgery, School of Stomatology, Nanjing 
      Medical University, Nanjing 210029, Jiangsu Province, China; Institute of 
      Stomatology, School of Stomatology, Nanjing Medical University, Nanjing 210029, 
      Jiangsu Province, China. Electronic address: jhb@njmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140711
PL  - Netherlands
TA  - Int J Biochem Cell Biol
JT  - The international journal of biochemistry & cell biology
JID - 9508482
RN  - 0 (Core Binding Factor Alpha 1 Subunit)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Histones)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Runx2 protein, rat)
RN  - 614OI1Z5WI (Valproic Acid)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
MH  - Acetylation
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Blotting, Western
MH  - *Cell Differentiation
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Chromatin Immunoprecipitation
MH  - Core Binding Factor Alpha 1 Subunit/genetics/*metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Fluorescent Antibody Technique
MH  - Histone Deacetylases/chemistry/genetics/*metabolism
MH  - Histones/*antagonists & inhibitors/metabolism
MH  - Immunoprecipitation
MH  - Male
MH  - Mesenchymal Stem Cells/*cytology/drug effects/metabolism
MH  - Osteogenesis/drug effects/*physiology
MH  - RNA, Messenger/genetics
MH  - RNA, Small Interfering/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Valproic Acid/pharmacology
OTO - NOTNLM
OT  - Bone marrow stromal cells
OT  - HDAC inhibitor
OT  - Histone H3 lysine 9 acetylation
OT  - Histone deacetylase 8
OT  - Osteogenic differentiation
EDAT- 2014/07/16 06:00
MHDA- 2015/05/23 06:00
CRDT- 2014/07/15 06:00
PHST- 2014/02/07 00:00 [received]
PHST- 2014/06/20 00:00 [revised]
PHST- 2014/07/03 00:00 [accepted]
PHST- 2014/07/15 06:00 [entrez]
PHST- 2014/07/16 06:00 [pubmed]
PHST- 2015/05/23 06:00 [medline]
AID - S1357-2725(14)00222-2 [pii]
AID - 10.1016/j.biocel.2014.07.003 [doi]
PST - ppublish
SO  - Int J Biochem Cell Biol. 2014 Sep;54:68-77. doi: 10.1016/j.biocel.2014.07.003. 
      Epub 2014 Jul 11.