PMID- 23376013
OWN - NLM
STAT- MEDLINE
DCOM- 20130919
LR  - 20220408
IS  - 1522-9653 (Electronic)
IS  - 1063-4584 (Linking)
VI  - 21
IP  - 4
DP  - 2013 Apr
TI  - Gene expression profiling of dedifferentiated human articular chondrocytes 
      in monolayer culture.
PG  - 599-603
LID - S1063-4584(13)00038-1 [pii]
LID - 10.1016/j.joca.2013.01.014 [doi]
AB  - OBJECTIVE: When primary chondrocytes are cultured in monolayer, they undergo 
      dedifferentiation during which they lose their phenotype and their capacity to 
      form cartilage. Dedifferentiation is an obstacle for cell therapy for cartilage 
      degeneration. In this study, we aimed to systemically evaluate the changes in 
      gene expression during dedifferentiation of human articular chondrocytes to 
      identify underlying mechanisms. METHODS: RNA was isolated from monolayer-cultured 
      primary human articular chondrocytes at serial passages. Gene expression was 
      analyzed by microarray. Based on the microarray analysis, relevant genes and 
      pathways were identified. Their functions in chondrocyte dedifferentiation were 
      further investigated. RESULTS: In vitro expanded human chondrocytes showed 
      progressive changes in gene expression. Strikingly, an overall decrease in total 
      gene expression was detected, which was both gradual and cumulative. DNA 
      methylation was in part responsible for the expression downregulation of a number 
      of genes. Genes involved in many pathways such as the 
      extracellular-signal-regulated kinase (ERK) and Bone morphogenetic protein (BMP) 
      pathways exhibited significant changes in expression. Inhibition of ERK pathway 
      did not show dramatic effects in counteracting dedifferentiation process. BMP-2 
      was able to decelerate the dedifferentiation and reinforce the maintenance of 
      chondrocyte phenotype in monolayer culture. CONCLUSION: Our study not only 
      improves our knowledge of the intricate signaling network regulating maintenance 
      of chondrocyte phenotype, but also contributes to improved chondrocyte expansion 
      and chondrogenic performance for cell therapy.
CI  - Copyright (c) 2013 Osteoarthritis Research Society International. Published by 
      Elsevier Ltd. All rights reserved.
FAU - Ma, B
AU  - Ma B
AD  - Department of Developmental BioEngineering, University of Twente, Enschede, The 
      Netherlands.
FAU - Leijten, J C H
AU  - Leijten JC
FAU - Wu, L
AU  - Wu L
FAU - Kip, M
AU  - Kip M
FAU - van Blitterswijk, C A
AU  - van Blitterswijk CA
FAU - Post, J N
AU  - Post JN
FAU - Karperien, M
AU  - Karperien M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130130
PL  - England
TA  - Osteoarthritis Cartilage
JT  - Osteoarthritis and cartilage
JID - 9305697
RN  - 0 (Bone Morphogenetic Proteins)
SB  - IM
MH  - Aged
MH  - Bone Morphogenetic Proteins/physiology
MH  - Cartilage, Articular/*cytology
MH  - Cell Differentiation/genetics/physiology
MH  - Cells, Cultured
MH  - Chondrocytes/*cytology
MH  - DNA Methylation
MH  - Gene Expression Profiling/methods
MH  - Gene Expression Regulation/physiology
MH  - Humans
MH  - MAP Kinase Signaling System/physiology
MH  - Middle Aged
MH  - Oligonucleotide Array Sequence Analysis/methods
EDAT- 2013/02/05 06:00
MHDA- 2013/09/21 06:00
CRDT- 2013/02/05 06:00
PHST- 2012/06/15 00:00 [received]
PHST- 2013/01/08 00:00 [revised]
PHST- 2013/01/12 00:00 [accepted]
PHST- 2013/02/05 06:00 [entrez]
PHST- 2013/02/05 06:00 [pubmed]
PHST- 2013/09/21 06:00 [medline]
AID - S1063-4584(13)00038-1 [pii]
AID - 10.1016/j.joca.2013.01.014 [doi]
PST - ppublish
SO  - Osteoarthritis Cartilage. 2013 Apr;21(4):599-603. doi: 
      10.1016/j.joca.2013.01.014. Epub 2013 Jan 30.