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.
Keywords: BMP-7; TGF-β1 signaling; Wnt/β-catenin signaling; cementoblastic differentiation; human periodontal ligament cells; ligament-fibroblastic differentiation.
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