The crosstalk between transforming growth factor-β1 and delta like-1 mediates early chondrogenesis during embryonic endochondral ossification.

Taipaleenmaki, Hanna, Harkness, Linda, Chen, Li, Larsen, Kenneth H., Saamanen, Anna-Marja, Kassem, Moustapha and Abdallah, Basem M. (2012) The crosstalk between transforming growth factor-β1 and delta like-1 mediates early chondrogenesis during embryonic endochondral ossification.. Stem Cells, 30 2: 304-313. doi:10.1002/stem.792


Author Taipaleenmaki, Hanna
Harkness, Linda
Chen, Li
Larsen, Kenneth H.
Saamanen, Anna-Marja
Kassem, Moustapha
Abdallah, Basem M.
Title The crosstalk between transforming growth factor-β1 and delta like-1 mediates early chondrogenesis during embryonic endochondral ossification.
Journal name Stem Cells   Check publisher's open access policy
ISSN 1066-5099
1549-4918
Publication date 2012
Year available 2012
Sub-type Article (original research)
DOI 10.1002/stem.792
Volume 30
Issue 2
Start page 304
End page 313
Total pages 10
Place of publication Durham, NC United States
Publisher AlphaMed Press
Language eng
Formatted abstract
Delta like-1 (Dlk1)/preadipocyte factor-1 (Pref-1)/fetal antigen-1 (FA1) is a novel surface marker for embryonic chondroprogenitor cells undergoing lineage progression from proliferation to prehypertrophic stages. However, mechanisms mediating control of its expression during chondrogenesis are not known. Thus, we examined the effect of a number of signaling molecules and their inhibitors on Dlk1 expression during in vitro chondrogenic differentiation in mouse embryonic limb bud mesenchymal micromass cultures and mouse embryonic fibroblast (MEF) pellet cultures. Dlk1/Pref-1 was initially expressed during mesenchymal condensation and chondrocyte proliferation, in parallel with expression of Sox9 and Col2a1, and was downregulated upon the expression of Col10a1 by hypertrophic chondrocytes. Among a number of molecules that affected chondrogenesis, transforming growth factor-β1 (TGF-β1)-induced proliferation of chondroprogenitors was associated with decreased Dlk1 expression. This effect was abolished by TGF-β signaling inhibitor SB431542, suggesting regulation of Dlk1/FA1 by TGF-β1 signaling in chondrogenesis. TGF-β1-induced Smad phosphorylation and chondrogenesis were significantly increased in Dlk1−/− MEF, while they were blocked in Dlk1 overexpressing MEF, in comparison with wild-type MEF. Furthermore, overexpression of Dlk1 or addition of its secreted form FA1 dramatically inhibited TGF-β1-induced Smad reporter activity. In conclusion, our data identified Dlk1/FA1 as a downstream target of TGF-β1 signaling molecule that mediates its function in embryonic chondrogenesis. The crosstalk between TGF-β1 and Dlk1/FA1 was shown to promote early chondrogenesis during the embryonic endochondral ossification process
Keyword Chondrogenesis
Signalling
Transforming growth factor β1
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Australian Institute for Bioengineering and Nanotechnology Publications
 
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Created: Wed, 23 Sep 2015, 15:19:37 EST by Linda Harkness on behalf of Aust Institute for Bioengineering & Nanotechnology