ZEB1 interferes with human periodontal ligament stem cell proliferation and differentiation

Abstract Background Periodontitis can eventually contribute to tooth loss. Zinc finger E‐box binding homeobox 1 (ZEB1) is identified as overexpressed in the gingival tissue of mice with periodontitis. This study is designed to decipher the mechanism of ZEB1's involvement in periodontitis. Methods Human periodontal mesenchymal stem cells (hPDLSCs) were exposed to LPS to mimic the inflammation in periodontitis. Following ZEB1 silencing, FX1 (an inhibitor of Bcl‐6) treatment or ROCK1 overexpression, cell viability, and apoptosis were analyzed. Alkaline phosphatase (ALP) staining, Alizarin red staining, RT‐qPCR, and western blot were performed to evaluate osteogenic differentiation and mineralization. hPDLSCs were processed for luciferase reporter assay and ChIP‐PCR to confirm the association between ZEB1 and ROCK1. Results The induction of ZEB1 silencing resulted in reduced cell apoptosis, enhanced osteogenic differentiation, and mineralization. Nevertheless, these effects were significantly blunted by FX1. ZEB1 was confirmed to bind to the promoter sites of ROCK1 and regulate the ROCK1/AMPK. Whereas ROCK1 overexpression reversed the effects of ZEB1 silencing on Bcl‐6/STAT1, as well as cell proliferation and osteogenesis differentiation. Conclusion hPDLSCs displayed decreased proliferation and weakened osteogenesis differentiation in response to LPS. These impacts were mediated by ZEB1 regulating Bcl‐6/STAT1 via AMPK/ROCK1.