https://orcid.org/0000-0002-9110-3675
Abstract
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.
Human periodontal ligament cells (hPDLCs) are cytodifferentiated into cementoblasts or ligaments progenitors, both of which can form tissues that hold tooth muscles to the pubic bone. This study deals with the control mechanism for how two different types of cytodifferentiation occur in undifferentiated hPDLCs. The β-catenin activation is necessary for ligament-fibroblastic differentiation. The β-catenin activation was induced by the TGF-β1 signal and can be accomplished by two processes: Suppression of DKK1, an antagonistic factor of Wnt signaling and nuclear translocation of β-catenin by association with the phosphorylated Smad3. Conversely, BMP7 treatment accompanied by blocking of TGF-β1 signaling is essential for cementoblastic differentiation. These findings explain that the presence of TGF-β1 stimuli determines whether hPDLCs can be differentiated into either ligament progenitors or cementoblasts.
