Integrating the findings from the aforementioned mechanism investigations with those of a series of rescue experiments and osteogenic differentiation cultures, we have substantiated that ITGB3-KD potentiates osteogenic differentiation and exerts proapoptotic radiosensitizing effects in osteosarcoma by activating the JNK/c-JUN/RUNX2 pathway. Here, MAPK8 is linked to osteosarcoma.