FTO-Mediated MMP1 m6A Modification Promotes Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells via the ERK Pathway in Congenital Scoliosis
The imbalance in the differentiation potential of bone marrow mesenchymal stem cells (BMSCs) impacts bone development, metabolism, and bone marrow microenvironment homeostasis. Despite this, the mechanism of action of BMSCs on congenital scoliosis (CS) is unclear. Therefore, expounding on its corresponding impact and mechanism has become the focus of our research. N6-methyladenosine (m6A) is the most common post-transcriptional modification in eukaryotic cells. The role of fat mass and obesity-related genes (FTO) in regulating BMSCs differentiation remains unclear. We used CS-derived samples to determine changes in mRNA and protein levels of genes associated with BMSCs differentiation. Our results suggest that FTO inhibits the osteogenic differentiation of BMSCs and promotes adipogenic differentiation of BMSCs. At the same time, MMP1 overexpression supports osteogenic differentiation of BMSCs, while MMP1 knockdown exerts an inhibitory effect. PD98059, a selective ERG inhibitor, blocks MMP1-mediated promotion. In addition, our results demonstrated that FTO affects the differentiation ability of BMSCs in CS patients by regulating MMP1 expression. FTO-mediated MMP1 m6A modification underlies MMP1's promotion of osteogenic differentiation via the ERK pathway, suggesting it might be a potential therapeutic target for CS.