FOXO1 regulates osteogenic differentiation of periodontal ligament stem cells through the METTL3 signaling pathway

Background: Periodontitis is a chronic inflammation that occurs in periodontal tissue and has a high incidence rate. Periodontal ligament stem cells (PDLSCs) are ideal candidates for periodontal tissue and bone regeneration in patients with periodontitis. The purpose of this work was to analyze the molecular mechanisms that affect the osteogenic differentiation of PDLSCs. Methods: In this work, qRT‒PCR was used to detect the mRNA expression level of FOXO1 in clinical tissues and PDLSCs. Alkaline phosphatase (ALP) staining and Alizarin red S (ARS) staining were used to detect the degree of osteogenic differentiation of PDLSCs. qRT‒PCR and western blotting were used to measure the levels of the early osteogenic markers COL1A1 and RUNX2. The JASPAR online database was used to predict FOXO1-regulated genes. Results: FOXO1 was generally expressed at low levels in clinical samples from patients with periodontitis. We provided evidence that overexpression of FOXO1 promoted osteogenic differentiation in PDLSCs. In addition, both in vitro and rescue experiments showed that FOXO1 regulated METTL3. FOXO1 affected osteogenic differentiation mainly by regulating METTL3 modification of the PI3K/AKT pathway. Conclusions: FOXO1 activated the PI3K/AKT signaling pathway by transcriptionally activating METTL3. This effect promoted the osteogenic differentiation of PDLSCs.