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The Cross-talk Between TGF-β1 and Dlk1 Mediates Early Chondrogenesis During Embryonic Endochondral Ossification.
MedLine Citation:
PMID:  22102178     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Dlkl/Pref-1/FA1 (delta like-1/preadipocyte factor-1/Fetal Antigen-1) 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 signalling 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 was initially expressed during mesenchymal condensation and chondrocyte proliferation, in parallel with expression of Sox9 and Col2a1, and was down-regulated upon the expression of Col10a1 by hypertrophic chondrocytes. Among a number of molecules that affected chondrogenesis, TGF-β1-induced proliferation of chondroprogenitors was associated with decreased Dlk1 expression. This effect was abolished by TGF-β signalling inhibitor SB431542, suggesting regulation of Dlk1/FA1 by TGF-β1 signalling 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 to 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 signalling molecule that mediates its function in embryonic chondrogenesis. The cross-talk between TGF-β1 and Dlk1/FA1 was shown to promote early chondrogenesis during the embryonic endochondral ossification process.
Authors:
Hanna Taipaleenmäki; Linda Harkness; Li Chen; Kenneth H Larsen; Anna-Marja Säämänen; Moustapha Kassem; Basem M Abdallah
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-18
Journal Detail:
Title:  Stem cells (Dayton, Ohio)     Volume:  -     ISSN:  1549-4918     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9304532     Medline TA:  Stem Cells     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 AlphaMed Press.
Affiliation:
Endocrine Research Laboratory (KMEB), Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark; Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland.
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