Y-Box-Binding Protein 1 Facilitates the Proliferation and Osteogenic Differentiation of Periodontal Ligament Stem Cells Through the Transcriptional Activation of FGF2-Mediated Akt/GSK3β/β-Catenin Signaling.

Abstract

Periodontal ligament stem cells (PDLSCs) are derived from periodontal tissue and can differentiate into osteoblasts, which are ideal materials for alveolar bone repair and periodontal tissue regeneration. In this study, we aimed to explore the effects of Y-box binding protein 1 (YB-1) on the osteogenic differentiation and proliferation of PDLSCs and its underlying mechanism. hPDLSC proliferation was detected by CCK-8 and EdU assays. The osteogenic differentiation of hPDLSCs was clarified using alkaline phosphatase (ALP) activity detection and Alizarin red S (ARS) staining. The expression levels of osteogenic differentiation-related factors, Akt/GSK3β/β-catenin pathway-related factors, YB-1, and fibroblast growth factor 2 (FGF2) were evaluated using qPCR and Western blotting. The interplay between YB-1 and FGF2 was clarified using ChIP and dual-luciferase reporter gene assays. YB-1 expression was markedly decreased in periodontitis clinical tissues but increased in hPDLSCs during osteogenic differentiation. Moreover, silencing YB-1 suppressed the osteogenic differentiation and proliferation of hPDLSCs. In addition, YB-1 promotes hPDLSC proliferation and osteogenic differentiation in a manner dependent on the activation of the Akt/GSK3β/β-catenin signaling pathway, which is mediated by FGF2 transcriptional activation. Furthermore, the inhibitory effects of YB-1 knockdown on the osteogenic differentiation and proliferation of hPDLSCs were antagonized by human recombinant FGF2. Taken together, our findings revealed that YB-1 facilitates hPDLSC proliferation and osteogenic differentiation through increasing the level of FGF2 via transcriptional regulation, thereby activating the Akt/GSK3β/β-catenin pathway.