Activation of β-catenin by TGF-β1 promotes ligament-fibroblastic differentiation and inhibits cementoblastic differentiation of human periodontal ligament cells.
Jong-Chan LimSang-Hoon BaeGyutae LeeChun Jeih RyuYoung-Joo JangPublished in: Stem cells (Dayton, Ohio) (2020)
TGF-β and Wnt/β-catenin signaling pathways are known to be essential for the development of periodontal tissue. In this study, we examined the crosstalk between TGF-β and Wnt/β-catenin signaling in ligament-fibroblastic differentiation of human periodontal ligament cells (hPDLCs). TGF-β1 treatment significantly increased the expression of ligament-fibroblastic markers, but such expression was preventing by treatment with SB431542, a TGF-β type I receptor inhibitor. As well as phosphorylation of Smad3, TGF-β1 increased β-catenin activation. The depletion of β-catenin reduced the expression of ligament-fibroblastic markers, suggesting that β-catenin is essential for ligament differentiation. The effect of TGF-β1 on β-catenin activation did not seem to be much correlated with Wnt stimuli, but endogenous DKK1 was suppressed by TGF-β1, indicating that β-catenin activation could be increased much more by TGF-β1. In addition to DKK1 suppression, Smad3 phosphorylation by TGF-β1 facilitated the nuclear translocation of cytoplasmic β-catenin. In contrast to ligament-fibroblastic differentiation, inhibition of TGF-β1 signaling was needed for cementoblastic differentiation of hPDLCs. BMP7 treatment accompanied by inhibition of TGF-β1 signaling had a synergistic effect on cementoblastic differentiation. In conclusion, β-catenin activation by TGF-β1 caused ligament-fibroblastic differentiation of hPDLCs, and the presence of TGF-β1 stimuli basically determined whether hPDLCs are differentiated into ligament progenitor or cementoblasts.
Keyphrases
- transforming growth factor
- epithelial mesenchymal transition
- cell proliferation
- signaling pathway
- stem cells
- endothelial cells
- induced apoptosis
- mesenchymal stem cells
- anterior cruciate ligament
- bone marrow
- magnetic resonance imaging
- cell death
- induced pluripotent stem cells
- endoplasmic reticulum stress
- smoking cessation