Details

Autor(en) / Beteiligte

• Taipaleenmäki, Hanna
• Harkness, Linda
• Chen, Li
• Larsen, Kenneth H.
• Säämänen, Anna-Marja
• Kassem, Moustapha
• Abdallah, Basem M.

Titel

The Crosstalk Between Transforming Growth Factor-β1 and Delta Like-1 Mediates Early Chondrogenesis During Embryonic Endochondral Ossification

Ist Teil von

• Stem cells (Dayton, Ohio), 2012-02, Vol.30 (2), p.304-313

Ort / Verlag

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. STEM CELLS 2012; 30:304–313.