DJ-1 promotes angiogenesis and osteogenesis by activating FGF receptor-1 signaling

Jung-Min Kim, Hong-In Shin, Sun-Shin Cha, Chang Sup Lee, Bok Sil Hong, Seyoung Lim, Hyun-Jun Jang, Jaeyoon Kim, Yong Ryoul Yang, Yun-Hee Kim, Sanguk Yun, Girdhari Rijal, Whaseon Lee-Kwon, Jeong Kon Seo, Yong Song Gho, Sung Ho Ryu, Eun-Mi Hur and Pann-Ghill Suh ()
Additional contact information
Jung-Min Kim: School of Nano-Bioscience & Chemical Engineering, Ulsan National Institute of Science and Technology, UNIST-gil 50, Ulsan 689-798, Republic of Korea.
Hong-In Shin: IHBR, School of Dentistry, Kyungpook National University, 2177 Dalgubeol-daero, Daegu 700-412, Republic of Korea.
Sun-Shin Cha: Korea Institute of Ocean Science and Technology (KIOST), 787 Haean-ro, Ansan 426-744, Republic of Korea.
Chang Sup Lee: Immunology, and Cancer Biology, University of Virginia, 1340 JPA, Charlottesville, Virginia 22908, USA.
Bok Sil Hong: Pohang University of Science and Technology, 77 Cheongam-ro, Pohang 790-784, Republic of Korea.
Seyoung Lim: School of Nano-Bioscience & Chemical Engineering, Ulsan National Institute of Science and Technology, UNIST-gil 50, Ulsan 689-798, Republic of Korea.
Hyun-Jun Jang: School of Nano-Bioscience & Chemical Engineering, Ulsan National Institute of Science and Technology, UNIST-gil 50, Ulsan 689-798, Republic of Korea.
Jaeyoon Kim: Pohang University of Science and Technology, 77 Cheongam-ro, Pohang 790-784, Republic of Korea.
Yong Ryoul Yang: School of Nano-Bioscience & Chemical Engineering, Ulsan National Institute of Science and Technology, UNIST-gil 50, Ulsan 689-798, Republic of Korea.
Yun-Hee Kim: National Cancer Center, 323 Ilsan-ro, Goyang 410-769, Republic of Korea.
Sanguk Yun: Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA.
Girdhari Rijal: IHBR, School of Dentistry, Kyungpook National University, 2177 Dalgubeol-daero, Daegu 700-412, Republic of Korea.
Whaseon Lee-Kwon: School of Nano-Bioscience & Chemical Engineering, Ulsan National Institute of Science and Technology, UNIST-gil 50, Ulsan 689-798, Republic of Korea.
Jeong Kon Seo: School of Nano-Bioscience & Chemical Engineering, Ulsan National Institute of Science and Technology, UNIST-gil 50, Ulsan 689-798, Republic of Korea.
Yong Song Gho: Pohang University of Science and Technology, 77 Cheongam-ro, Pohang 790-784, Republic of Korea.
Sung Ho Ryu: Pohang University of Science and Technology, 77 Cheongam-ro, Pohang 790-784, Republic of Korea.
Eun-Mi Hur: Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seoul 136-791, Republic of Korea.
Pann-Ghill Suh: School of Nano-Bioscience & Chemical Engineering, Ulsan National Institute of Science and Technology, UNIST-gil 50, Ulsan 689-798, Republic of Korea.

Nature Communications, 2012, vol. 3, issue 1, 1-11

Abstract: 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.

Date: 2012
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DOI: 10.1038/ncomms2313

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