scholarly journals TGF-β regulates phosphorylation and stabilization of Sox9 protein in chondrocytes through p38 and Smad dependent mechanisms

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
George Coricor ◽  
Rosa Serra
Keyword(s):  
2002 ◽  
Vol 50 (8) ◽  
pp. 1059-1065 ◽  
Author(s):  
Sherri R. Davies ◽  
Shinji Sakano ◽  
Yong Zhu ◽  
Linda J. Sandell

The control of extracellular matrix (ECM) production is important for the development, maintenance, and repair of cartilage tissues. Matrix molecule synthesis is generally regulated by the rate of gene transcription determined by DNA transcription factors. We have shown that transcription factors Sox9, AP-2, and [delta]EF1 are able to alter the rate of CD-RAP transcription in vitro: Sox9 upregulates, AP-2 exhibits biphasic effects, and [delta]EF1 represses expression of the CD-RAP gene. To correlate these in vitro activities in vivo, transcription factors were co-immunolocalized with ECM proteins in three different cartilage tissues in which the rates of biosynthesis are quite different: articular, meniscal, and growth plate. Immunoreactivities of type II collagen and CD-RAP were higher in growth plate than in either the articular or meniscal cartilages and correlated positively with Sox9 protein. Sox9 staining decreased with hypertrophy and was low in articular and meniscal cartilages. In contrast, AP-2 and [delta]EF1 were low in proliferating chondrocytes but high in lower growth plate, articular, and meniscal cartilages. This increase was also accompanied by intense nuclear staining. These immunohistochemical results are the first to localize both [delta]EF1 and AP-2 to adult articular, meniscal, and growth plate cartilages and provide in vivo correlation of previous molecular biological studies.


2001 ◽  
Vol 169 (3) ◽  
pp. 573-579 ◽  
Author(s):  
I Sekiya ◽  
P Koopman ◽  
K Tsuji ◽  
S Mertin ◽  
V Harley ◽  
...  

SOX9 is a transcription factor that activates type II procollagen (Col2a1) gene expression during chondrocyte differentiation. Glucocorticoids are also known to promote chondrocyte differentiation via unknown molecular mechanisms. We therefore investigated the effects of a synthetic glucocorticoid, dexamethasone (DEX), on Sox9 gene expression in chondrocytes prepared from rib cartilage of newborn mice. Sox9 mRNA was expressed at high levels in these chondrocytes. Treatment with DEX enhanced Sox9 mRNA expression within 24 h and this effect was observed at least up to 48 h. The effect of DEX was dose dependent, starting at 0.1 nM and maximal at 10 nM. The half life of Sox9 mRNA was approximately 45 min in the presence or absence of DEX. Western blot analysis revealed that DEX also enhanced the levels of SOX9 protein expression. Treatment with DEX enhanced Col2a1 mRNA expression in these chondrocytes and furthermore, DEX enhanced the activity of Col2-CAT (chloramphenicol acetyltransferase) construct containing a 1.6 kb intron fragment where chondrocyte-specific Sry/Sox- consensus sequence is located. The enhancing effect of DEX was specific to SOX9, as DEX did not alter the levels of Sox6 mRNA expression. These data suggest that DEX promotes chondrocyte differentiation through enhancement of SOX9.


2015 ◽  
Vol 212 (12) ◽  
pp. 2057-2075 ◽  
Author(s):  
Aurélie Ladang ◽  
Francesca Rapino ◽  
Lukas C. Heukamp ◽  
Lars Tharun ◽  
Kateryna Shostak ◽  
...  

Tumor initiation in the intestine can rapidly occur from Lgr5+ crypt columnar stem cells. Dclk1 is a marker of differentiated Tuft cells and, when coexpressed with Lgr5, also marks intestinal cancer stem cells. Here, we show that Elp3, the catalytic subunit of the Elongator complex, is required for Wnt-driven intestinal tumor initiation and radiation-induced regeneration by maintaining a subpool of Lgr5+/Dclk1+/Sox9+ cells. Elp3 deficiency dramatically delayed tumor appearance in Apc-mutated intestinal epithelia and greatly prolonged mice survival without affecting the normal epithelium. Specific ablation of Elp3 in Lgr5+ cells resulted in marked reduction of polyp formation upon Apc inactivation, in part due to a decreased number of Lgr5+/Dclk1+/Sox9+ cells. Mechanistically, Elp3 is induced by Wnt signaling and promotes Sox9 translation, which is needed to maintain the subpool of Lgr5+/Dclk1+ cancer stem cells. Consequently, Elp3 or Sox9 depletion led to similar defects in Dclk1+ cancer stem cells in ex vivo organoids. Finally, Elp3 deficiency strongly impaired radiation-induced intestinal regeneration, in part because of decreased Sox9 protein levels. Together, our data demonstrate the crucial role of Elp3 in maintaining a subpopulation of Lgr5-derived and Sox9-expressing cells needed to trigger Wnt-driven tumor initiation in the intestine.


2016 ◽  
Vol 48 (6) ◽  
pp. 3111-3120 ◽  
Author(s):  
Maciej Kamaszewski ◽  
Aleksandra Gosk ◽  
Marek Skrobisz ◽  
Teresa Ostaszewska

2006 ◽  
Vol 6 (7) ◽  
pp. 695-702 ◽  
Author(s):  
Cécile Notarnicola ◽  
Safia Malki ◽  
Philippe Berta ◽  
Francis Poulat ◽  
Brigitte Boizet-Bonhoure

2011 ◽  
Vol 286 (37) ◽  
pp. 32162-32169 ◽  
Author(s):  
Seiji Kishi ◽  
Hideharu Abe ◽  
Haruhiko Akiyama ◽  
Tatsuya Tominaga ◽  
Taichi Murakami ◽  
...  

2013 ◽  
Vol 288 (49) ◽  
pp. 35138-35148 ◽  
Author(s):  
Takako Hattori ◽  
Tetsuya Kishino ◽  
Shelley Stephen ◽  
Heidi Eberspaecher ◽  
Sayumi Maki ◽  
...  

2000 ◽  
Vol 113 (1) ◽  
pp. 31-36 ◽  
Author(s):  
K. Fröjdman ◽  
V. R. Harley ◽  
L. J. Pelliniemi
Keyword(s):  

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