Nevertheless, we provided both in vitro and in vivo evidence that OPLL patient’s spinal ligament cell-derived small EVs contribute to the development of OPLL by promoting the osteogenic differentiation of MSCs and ligaments while inhibiting osteoclast formation, the molecular mechanism of which is largely due to EV-transmitted miR-320e modulation of TAK1 signaling in both ligament cells and MSCs. Here, MAP3K7 is linked to ossification of the posterior longitudinal ligament of the spine.