Our findings indicate that ITGB3-KD enhances radiosensitivity in osteosarcoma by promoting osteogenic differentiation and apoptosis through activation of the JNK/c-JUN/RUNX2 pathway, identifying ITGB3 as a candidate therapeutic target and implicating JNK/c-JUN/RUNX2 signaling as a modulatory axis for improving the response to radiation of osteosarcoma. This evidence concerns the gene MAPK8 and osteosarcoma.