PMID- 28220902
OWN - NLM
STAT- MEDLINE
DCOM- 20181030
LR  - 20181113
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
DP  - 2017 Feb 21
TI  - TWIST1 induces MMP3 expression through up-regulating DNA hydroxymethylation and 
      promotes catabolic responses in human chondrocytes.
PG  - 42990
LID - 10.1038/srep42990 [doi]
LID - 42990
AB  - The objective was to investigate the levels of TWIST1 in normal and OA cartilage 
      and examine its role in regulating gene expression in chondrocytes. Human 
      cartilage tissues and chondrocytes were obtained at autopsy from normal knee 
      joints and from OA-affected joints at the time of total knee arthroplasty. TWIST1 
      expression was increased in human OA knee cartilage compared to normal knee 
      cartilage. TWIST1 induced matrix metalloproteinase 3 (MMP3) expression without 
      direct binding to MMP3 promoter and increased the 5-hydroxymethylcytosine (5hmC) 
      level at the MMP3 promoter. The effect of TWIST1 on expression of TET family 
      (TET1, 2 and 3) was measured in stable TWIST1 transfected TC28 cells, and TET1 
      expression was up-regulated. TWIST1 dependent upregulation of Mmp3 expression was 
      suppressed in Tet triple KO fibroblast derived from mouse ES cells. Increased 
      TWIST1 expression is a feature of OA-affected cartilage. We identified a novel 
      mechanism of catabolic reaction where TWIST1 up-regulates MMP3 expression by 
      enriching 5hmC levels at the MMP3 promoter via TET1 induction. These findings 
      implicate TWIST1 as an important factor regulating OA related gene expression. 
      Clarifying epigenetic mechanisms of 5hmC induced by TWIST1 is a critical molecule 
      to understanding OA pathogenesis.
FAU - Hasei, Joe
AU  - Hasei J
AD  - Department of Molecular and Experimental Medicine, The Scripps Research 
      Institute, La Jolla, CA, USA.
FAU - Teramura, Takeshi
AU  - Teramura T
AD  - Department of Molecular and Experimental Medicine, The Scripps Research 
      Institute, La Jolla, CA, USA.
AD  - Division of Cell Biology for Regenerative Medicine, Institute of Advanced 
      Clinical Medicine, Kindai University, Faculty of Medicine, Osaka, Japan.
FAU - Takehara, Toshiyuki
AU  - Takehara T
AD  - Division of Cell Biology for Regenerative Medicine, Institute of Advanced 
      Clinical Medicine, Kindai University, Faculty of Medicine, Osaka, Japan.
FAU - Onodera, Yuta
AU  - Onodera Y
AD  - Division of Cell Biology for Regenerative Medicine, Institute of Advanced 
      Clinical Medicine, Kindai University, Faculty of Medicine, Osaka, Japan.
FAU - Horii, Takuro
AU  - Horii T
AD  - Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for 
      Molecular and Cellular Regulation, Gunma University, Gunma, Japan.
FAU - Olmer, Merissa
AU  - Olmer M
AD  - Department of Molecular and Experimental Medicine, The Scripps Research 
      Institute, La Jolla, CA, USA.
FAU - Hatada, Izuho
AU  - Hatada I
AD  - Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for 
      Molecular and Cellular Regulation, Gunma University, Gunma, Japan.
FAU - Fukuda, Kanji
AU  - Fukuda K
AD  - Division of Cell Biology for Regenerative Medicine, Institute of Advanced 
      Clinical Medicine, Kindai University, Faculty of Medicine, Osaka, Japan.
AD  - Department of Rehabilitation Medicine, Kindai University, Faculty of Medicine, 
      Osaka, Japan.
FAU - Ozaki, Toshifumi
AU  - Ozaki T
AD  - Science of Functional Recovery and Reconstruction, Okayama University Graduate 
      School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
FAU - Lotz, Martin K
AU  - Lotz MK
AD  - Department of Molecular and Experimental Medicine, The Scripps Research 
      Institute, La Jolla, CA, USA.
FAU - Asahara, Hiroshi
AU  - Asahara H
AD  - Department of Molecular and Experimental Medicine, The Scripps Research 
      Institute, La Jolla, CA, USA.
AD  - Department of Systems BioMedicine, Graduate School of Medical and Dental 
      Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
LA  - eng
GR  - P01 AG007996/AG/NIA NIH HHS/United States
GR  - R01 AG049617/AG/NIA NIH HHS/United States
GR  - R01 AR050631/AR/NIAMS NIH HHS/United States
GR  - R01 AR065379/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20170221
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (TWIST1 protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Twist-Related Protein 1)
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Cartilage, Articular/cytology/metabolism/pathology
MH  - Cells, Cultured
MH  - Chondrocytes/cytology/metabolism
MH  - DNA Methylation
MH  - Fibroblasts/cytology/metabolism
MH  - Humans
MH  - Matrix Metalloproteinase 3/genetics/*metabolism
MH  - Mice
MH  - Middle Aged
MH  - Nuclear Proteins/genetics/*metabolism
MH  - Osteoarthritis, Knee/metabolism/pathology
MH  - Promoter Regions, Genetic
MH  - Proto-Oncogene Proteins/antagonists & inhibitors/genetics/metabolism
MH  - RNA Interference
MH  - RNA, Small Interfering/metabolism
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Twist-Related Protein 1/genetics/*metabolism
MH  - Up-Regulation/drug effects
PMC - PMC5318945
COIS- The authors declare no competing financial interests.
EDAT- 2017/02/22 06:00
MHDA- 2018/10/31 06:00
PMCR- 2017/02/21
CRDT- 2017/02/22 06:00
PHST- 2016/05/16 00:00 [received]
PHST- 2017/01/18 00:00 [accepted]
PHST- 2017/02/22 06:00 [entrez]
PHST- 2017/02/22 06:00 [pubmed]
PHST- 2018/10/31 06:00 [medline]
PHST- 2017/02/21 00:00 [pmc-release]
AID - srep42990 [pii]
AID - 10.1038/srep42990 [doi]
PST - epublish
SO  - Sci Rep. 2017 Feb 21;7:42990. doi: 10.1038/srep42990.