Cell-to-cell communication facilitates the healing of bone fractures. By screening molecules secreted from human mesenchymal stem cells during osteogenesis, this study identified DJ1 as a novel angiogenic factor that mediated crosstalk between osteoblasts and endothelial cells, and promoted osteogenesis through the activation of fibroblast growth factor receptor 1 signalling. In a rodent model of bone fracture repair, application of DJ1 to the injured site increased bone regeneration by stimulating the formation of blood vessels and new bone, suggesting that targeting DJ1 could have therapeutic potential in bone fracture healing.