PMID- 26995110
OWN - NLM
STAT- MEDLINE
DCOM- 20180412
LR  - 20181202
IS  - 1522-9653 (Electronic)
IS  - 1063-4584 (Linking)
VI  - 24
IP  - 8
DP  - 2016 Aug
TI  - Neo-cartilage engineered from primary chondrocytes is epigenetically similar to 
      autologous cartilage, in contrast to using mesenchymal stem cells.
PG  - 1423-30
LID - S1063-4584(16)01070-0 [pii]
LID - 10.1016/j.joca.2016.03.009 [doi]
AB  - OBJECTIVES: To compare the epigenetic landscape of 3D cell models of human 
      primary articular chondrocytes (hPACs) and human bone-marrow derived mesenchymal 
      stem cells (hBMSCs) and their respective autologous articular cartilage. DESIGN: 
      Using Illumina Infinium HumanMethylation450 BeadChip arrays, the DNA methylation 
      landscape of the different cell sources and autologous cartilage was determined. 
      Pathway enrichment was analyzed using DAVID. RESULTS: Principal Component 
      Analysis (PCA) of methylation data revealed separate clustering of hBMSC samples. 
      Between hBMSCs and autologous cartilage 86,881 cytosine-phosphate-guanine 
      dinucleotides (CpGs) (20.2%), comprising 3,034 differentially methylated regions 
      (DMRs; Deltabeta > 0.1; with the same direction of effect), were significantly 
      differentially methylated. In contrast, between hPACs and autologous cartilage 
      only 5,706 CpGs (1.33%) were differentially methylated. Of interest was the 
      finding of the transcriptionally active, hyper-methylation of a Cartilage 
      Intermediate Layer Protein (CILP) annotated DMR (Deltabeta = 0.16) in PAC-cartilage, 
      corresponding to a profound decrease in CILP expression after in vitro culturing 
      of hPACs as compared to autologous cartilage. CONCLUSIONS: In vitro engineered 
      neo-cartilage tissue from primary chondrocytes, hPACs, exhibits a DNA methylation 
      landscape that is almost identical (99% similarity) to autologous cartilage, in 
      contrast to neo-cartilage engineered from bone marrow-derived mesenchymal stem 
      cells (MSCs). Although hBMSCs are widely used for cartilage engineering purposes 
      the effects of these vast differences on cartilage regeneration and long term 
      consequences of implantation, are not known. The use of hBMSCs or hPACs for 
      future cartilage tissue regeneration purposes should therefore be investigated in 
      more depth in future endeavors to better understand the consequences of the 
      differential methylome on neo-cartilage.
CI  - Copyright (c) 2016 Osteoarthritis Research Society International. Published by 
      Elsevier Ltd. All rights reserved.
FAU - Bomer, N
AU  - Bomer N
AD  - Dept. of Molecular Epidemiology, LUMC, Leiden, The Netherlands; IDEAL, LUMC, 
      Leiden, The Netherlands.
FAU - den Hollander, W
AU  - den Hollander W
AD  - Dept. of Molecular Epidemiology, LUMC, Leiden, The Netherlands.
FAU - Suchiman, H
AU  - Suchiman H
AD  - Dept. of Molecular Epidemiology, LUMC, Leiden, The Netherlands.
FAU - Houtman, E
AU  - Houtman E
AD  - Dept. of Molecular Epidemiology, LUMC, Leiden, The Netherlands.
FAU - Slieker, R C
AU  - Slieker RC
AD  - Dept. of Molecular Epidemiology, LUMC, Leiden, The Netherlands; IDEAL, LUMC, 
      Leiden, The Netherlands.
FAU - Heijmans, B T
AU  - Heijmans BT
AD  - Dept. of Molecular Epidemiology, LUMC, Leiden, The Netherlands; IDEAL, LUMC, 
      Leiden, The Netherlands.
FAU - Slagboom, P E
AU  - Slagboom PE
AD  - Dept. of Molecular Epidemiology, LUMC, Leiden, The Netherlands; IDEAL, LUMC, 
      Leiden, The Netherlands.
FAU - Nelissen, R G H H
AU  - Nelissen RG
AD  - Dept. of Orthopaedics, LUMC, Leiden, The Netherlands.
FAU - Ramos, Y F M
AU  - Ramos YF
AD  - Dept. of Molecular Epidemiology, LUMC, Leiden, The Netherlands.
FAU - Meulenbelt, I
AU  - Meulenbelt I
AD  - Dept. of Molecular Epidemiology, LUMC, Leiden, The Netherlands. Electronic 
      address: i.meulenbelt@lumc.nl.
LA  - eng
PT  - Journal Article
DEP - 20160317
PL  - England
TA  - Osteoarthritis Cartilage
JT  - Osteoarthritis and cartilage
JID - 9305697
SB  - IM
MH  - Cartilage, Articular
MH  - Chondrocytes
MH  - Humans
MH  - *Mesenchymal Stem Cells
MH  - Regeneration
MH  - Tissue Engineering
OTO - NOTNLM
OT  - Articular cartilage
OT  - Chondrocytes
OT  - DNA methylation
OT  - Stem cells
OT  - Tissue engineering
EDAT- 2016/03/21 06:00
MHDA- 2018/04/13 06:00
CRDT- 2016/03/21 06:00
PHST- 2015/12/22 00:00 [received]
PHST- 2016/02/16 00:00 [revised]
PHST- 2016/03/10 00:00 [accepted]
PHST- 2016/03/21 06:00 [entrez]
PHST- 2016/03/21 06:00 [pubmed]
PHST- 2018/04/13 06:00 [medline]
AID - S1063-4584(16)01070-0 [pii]
AID - 10.1016/j.joca.2016.03.009 [doi]
PST - ppublish
SO  - Osteoarthritis Cartilage. 2016 Aug;24(8):1423-30. doi: 
      10.1016/j.joca.2016.03.009. Epub 2016 Mar 17.