Previously, we developed a highly cell-adaptive dynamic hydrogel (HA-ADA) that modulates MSC fate through unknown mechanisms. Here, using human bone marrow-derived mesenchymal stem cells (hMSCs), we found that sustained mechanical stimulation provided by HA-ADA hydrogel induced rapid spreading and significantly enhanced their osteogenic differentiation while inhibiting adipogenesis. Mechanistically, miRNA sequencing revealed that this process was mediated by the downregulation of miR-376a-3p and miR-127-5p, thereby relieving their inhibitory effect on the methyltransferase SETD7. Elevated SETD7 expression catalyzed methylation of β-catenin and accelerated its nuclear translocation.
