FOXA1 knockdown alleviates inflammation and enhances osteogenic differentiation of periodontal ligament stem cells via STAT3 pathway.

Background: Evidence has confirmed that forkhead box protein A1 (FOXA1) inhibits the osteogenic differentiation of bone marrow mesenchymal stem cells. However, whether FOXA1 regulates the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) to participate in periodontitis process is unclear.

Methods: Lipopolysaccharide (LPS) was used to treat hPDLSCs to mimic inflammation environments. FOXA1 expression was examined by quantitative real-time PCR and western blot. The levels of IL-6 and TNF-α were evaluated by quantitative real-time PCR, ELISA and immunohistochemistry staining. hPDLSCs osteogenic differentiation was assessed by measuring alkaline phosphatase activity, alizarin red S intensity and the levels of osteogenic differentiation-related markers. Besides, the expression of signal transducer and activator of transcription 3 (STAT3) pathway-related markers were examined by western blot and immunofluorescence staining.

Results: FOXA1 was upregulated in the periodontal ligament tissues of periodontitis patients, and its knockdown enhanced osteogenic differentiation of hPDLSCs. Besides, downregulation of FOXA1 suppressed inflammation levels in LPS-induced hPDLSCs. Also, FOXA1 silencing promoted the osteogenic differentiation of LPS-induced hPDLSCs by the inactivation of STAT3 pathway.

Conclusion: Our data confirmed that knockdown of FOXA1 attenuated inflammation and enhanced osteogenic differentiation of LPS-induced hPDLSCs by regulating STAT3 pathway, indicating that FOXA1 might be a target for periodontitis treatment.