Abstract
Communication between osteoblasts and endothelial cells is essential for bone fracture repair, but the molecular identities of such communicating factors are not well defined. Here we identify DJ-1 as a novel mediator of the cross-talk between osteoblasts and endothelial cells through an unbiased screening of molecules secreted from human mesenchymal stem cells during osteogenesis. We show that DJ-1 stimulates the differentiation of human mesenchymal stem cells to osteoblasts and that DJ-1 induces angiogenesis in endothelial cells through activation of fibroblast growth factor receptor-1 signalling. In a rodent model of bone fracture repair, extracellular application of DJ-1 enhances bone regeneration in vivo by stimulating the formation of blood vessels and new bones. Both these effects are blocked by antagonizing fibroblast growth factor receptor-1 signalling. These findings uncover previously undefined extracellular roles of DJ-1 to promote angiogenesis and osteogenesis, suggesting DJ-1 may have therapeutic potential to stimulate bone regeneration.
| Original language | English |
|---|---|
| Article number | 1296 |
| Journal | Nature Communications |
| Volume | 3 |
| DOIs | |
| State | Published - 2012 |
Bibliographical note
Funding Information:We would like to thank Peter Parker at Cancer Research UK, H. Moo Kwon and Yoonkyung Do at UNIST and Seongho Ryu at Weill Cornell Medical College for critically reading of the manuscript. This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (KRF-2007-341-C00027) and the Pioneer Research Centre Programme through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2012-0000432) and S.-S. Cha was supported by a KIOST in-house NSC research programme, Republic of Korea.