PMID- 22653295
OWN - NLM
STAT- MEDLINE
DCOM- 20131017
LR  - 20220330
IS  - 1574-4647 (Electronic)
IS  - 0161-9152 (Print)
IS  - 0161-9152 (Linking)
VI  - 35
IP  - 4
DP  - 2013 Aug
TI  - Type II TGFbeta receptor modulates chondrocyte phenotype.
PG  - 1105-16
LID - 10.1007/s11357-012-9433-7 [doi]
AB  - Aging is one of the major risk factors of osteoarthritis. This pathology during 
      which chondrocytes undergo modifications of their phenotype may result from 
      alteration of transforming growth factor beta (TGFbeta) signaling. This study 
      investigates the role of TGFbeta response in the process of chondrocyte 
      dedifferentiation/redifferentiation. Dedifferentiation was induced by successive 
      passages of human articular chondrocytes, whereas their redifferentiation was 
      performed by three-dimensional culture in alginate. Human mesenchymal stem cells 
      were obtained from bone marrow and differentiated into chondrocyte-like phenotype 
      by three-dimensional culture, embedded in the same scaffold. Protein and mRNA 
      levels were analyzed by Western blot and real-time reverse transcription PCR. 
      Regulatory mechanism was investigated using specific inhibitors (mithramycin), 
      mRNA silencing or decoy oligonucleotides, and expression vectors. Chondrocyte 
      dedifferentiation interfered with TGFbeta signaling by decreasing TbetaRII mRNA and 
      protein levels and subsequent TGFbeta response. TbetaRII ectopic expression in passaged 
      chondrocytes permitted to increase the expression of several matrix genes, such 
      as aggrecan or type II collagen. Redifferentiation of passaged chondrocytes 
      permitted to restore, at least in part, TbetaRII expression and was related to 
      differentiation of human bone marrow mesenchymal stem cells toward chondrocytes, 
      where both specific protein 1 (Sp1) and TbetaRII mRNA levels were increased. 
      Moreover, Sp1 manipulation by silencing or ectopic expression and pharmacologic 
      inhibition revealed a link between expression levels of this transcriptional 
      factor, which is crucial for constitutive expression of TbetaRII in cartilage, and 
      TGFbeta response. Therefore, these data permit us to suggest an important role of 
      TbetaRII expression in the maintenance of chondrocyte phenotype, which is altered 
      with age, and bring new insights in our understanding of chondrogenesis process.
FAU - Bauge, Catherine
AU  - Bauge C
AD  - EA4652 Microenvironnement Cellulaire et Pathologies (MILPAT), Universite de Caen 
      Basse-Normandie, 14032, Caen cedex, France. catherine.bauge@unicaen.fr
FAU - Duval, Elise
AU  - Duval E
FAU - Ollitrault, David
AU  - Ollitrault D
FAU - Girard, Nicolas
AU  - Girard N
FAU - Leclercq, Sylvain
AU  - Leclercq S
FAU - Galera, Philippe
AU  - Galera P
FAU - Boumediene, Karim
AU  - Boumediene K
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120601
PL  - Netherlands
TA  - Age (Dordr)
JT  - Age (Dordrecht, Netherlands)
JID - 101250497
RN  - 0 (RNA, Messenger)
RN  - 0 (Transforming Growth Factor beta2)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Aging/*genetics/metabolism/pathology
MH  - Blotting, Western
MH  - Cartilage, Articular/*metabolism/pathology
MH  - Cell Differentiation/genetics
MH  - Cells, Cultured
MH  - Chondrocytes/*metabolism/pathology
MH  - Disease Progression
MH  - *Gene Expression Regulation
MH  - Humans
MH  - Middle Aged
MH  - Osteoarthritis, Hip/genetics/metabolism/pathology
MH  - Phenotype
MH  - RNA, Messenger/*genetics/metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Signal Transduction/genetics
MH  - Transforming Growth Factor beta2/biosynthesis/*genetics
PMC - PMC3705098
EDAT- 2012/06/02 06:00
MHDA- 2013/10/18 06:00
PMCR- 2014/08/01
CRDT- 2012/06/02 06:00
PHST- 2011/08/11 00:00 [received]
PHST- 2012/05/15 00:00 [accepted]
PHST- 2012/06/02 06:00 [entrez]
PHST- 2012/06/02 06:00 [pubmed]
PHST- 2013/10/18 06:00 [medline]
PHST- 2014/08/01 00:00 [pmc-release]
AID - 9433 [pii]
AID - 10.1007/s11357-012-9433-7 [doi]
PST - ppublish
SO  - Age (Dordr). 2013 Aug;35(4):1105-16. doi: 10.1007/s11357-012-9433-7. Epub 2012 
      Jun 1.