Effect Of FTO On Osteogenesis Of SCAPs In Inflammatory Microenvironment

Caries, pulpitis, periapical periodontitis and other injuries can cause inflammation of the pulp. It remains unclear how the inflammatory microenvironment affects the biological functions of stem cells from apical papilla (SCAPs), which have strong osteogenic differentiation ability. This study aims to clarify the effect of the inflammatory microenvironment on the osteogenic differentiation of SCAPs. We used LPS to simulate the inflammatory microenvironment in vitro. ALP stain, alizarin red stain, osteogenic-specific gene expression, and m6A related gene expression were analyzed. We performed knockout and overexpression of FTO under normal and inflammatory microenvironments, observed the changes in its osteogenic ability. FTO inhibitor were set up for further analysis. After LPS treated, the mRNA expression levels of osteogenic-related factors and FTO increased, and the ALP activity was enhanced. In the functional loss experiment, the mRNA levels of osteogenic-related factors and the ALP activity in the LPS + FTO-KO group were decreased. In the functional gain experiment, the transcription levels of osteogenic-related factors were up-regulated, the ALP activity and calcium nodule formation were increased. The effect of the FTO inhibitor was similar to that of FTO-KO group. LPS promotes the osteogenic differentiation of human SCAPs in vitro. FTO promotes the osteogenic differentiation of human SCAPs under the condition of the inflammatory microenvironment, and knockout FTO or adding an inhibitor can negatively regulate osteogenic differentiation, suggesting that FTO may be a potential therapeutic target for modulating SCAPs function in inflammatory dental disorders.