Effect of overexpression of KDM6B on gene expression in human periodontal ligament stem cells

In this study, we identify histone demethylase KDM6B as a critical regulator of osteogenic differentiation in mechanically stimulated periodontal ligament stem cells (PDLSCs). Prior sequencing initiatives and research have underscored KDM6B's mechanosensitivity and illuminated how advanced glycation end-products (AGEs) inhibit KDM6B, thereby impairing stem cell differentiation capabilities. Significant H3K27Me3 enrichment was observed at the transcriptional regions of osteogenic markers (ALP, RUNX2, BMP2, COL1A1) in pluripotent stem cells, with KDM6B essential for the demethylation of H3K27Me3. Moreover, KDM6B was found to activate several critical genes within both the canonical and non-canonical Wnt pathways, enhancing TCF and NFATC family gene expression and facilitating antioxidative responses, matrix adhesion, and intercellular interactions in PDLSCs. Collectively, our data establish a molecular framework that illustrates the cooperative role of lineage-specific histone modifiers in osteogenic differentiation, highlights KDM6B's function in eradicating repressive histone marks, and delineates a reciprocal enhancement loop involving KDM6B and the Wnt signaling pathways.