KLF2 Promotes Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Regulating Nrf2 Expression

OBJECTIVE: Periodontal ligament stem cells (PDLSCs) are emerging as a promising source for periodontal regeneration and to manage periodontitis. This study aims to investigate the roles of Krüppel-like factor 2 (KLF2) and nuclear factor erythroid 2-related factor (Nrf2) in mediating osteogenic differentiation of human PDLSCs (hPDLSCs) in the context of lipopolysaccharide (LPS) stimulation. METHODS: The osteogenic differentiation potential of hPDLSCs isolated from human premolar root samples were examined by alkaline phosphatase (ALP) staining and ALP activity assay, Alizarin red S staining and quantitative analysis of mineralised matrix. Intracellular reactive oxygen species (ROS) production and glutathione (GSH) concentration were assessed to reflect oxidative stress. RESULTS: KLF2 overexpression influenced Nrf2-regulated transcription, leading to significant increases in GSH concentration, ALP activity, mineralised matrix formation, and RUNX2 expression in LPS-stimulated hPDLSCs, as well as significant reductions in ROS production and cell apoptosis. The subsequent Nrf2 knockdown impaired the protective effect of KLF2 on hPDLSCs against LPS stimulation. CONCLUSION: The findings of the study demonstrate KLF2 overexpression has the ability to promote the osteogenic differentiation of hPDLSCs by promoting Nrf2 activation, suggesting that KLF2 mediating Nrf2 could be a promising target to facilitate the efficacy of PDLSC-based bone regeneration in periodontitis.