Osteosarcoma is the most common type of bone cancer and the second leading cause of cancer-related deaths in children and young adults [1]. The majority of osteosarcomas originate in the long bones, such as the distal femur and proximal tibia. It is highly aggressive with a metastatic rate of ~20%, with the most common targets being the lung and other bones [2]. Although the origins of osteosarcoma remain unclear, the most likely candidates are considered to be mesenchymal stem cells (MSCs) or osteoprogenitor cells [3] and [4]. Currently, the primary treatment for osteosarcoma is a combination of surgery and chemotherapy. However, osteosarcoma frequently develops resistance to conventional chemotherapies resulting in tumor recurrence. Amputation of the affected limbs is often the only option but even this usually fails to save a patient's life due to early metastases [5]. A better understanding of tumor pathology in osteosarcoma and the mechanisms of initiation and recurrence are urgently needed to improve patient prognosis.