title: DJ-1 promotes angiogenesis and osteogenesis by activating FGF receptor-1 signaling.
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.
authors.affiliation: School of Nano-Bioscience & Chemical Engineering, Ulsan National Institute of Science and Technology, UNIST-gil 50, Ulsan 689-798, Republic of Korea.
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Hong-In
authors.initials: HI
authors.lastname: Shin
authors.forename: Sun-Shin
authors.initials: SS
authors.lastname: Cha
authors.forename: Chang Sup
authors.initials: CS
authors.lastname: Lee
authors.forename: Bok Sil
authors.initials: BS
authors.lastname: Hong
authors.forename: Seyoung
authors.initials: S
authors.lastname: Lim
authors.forename: Hyun-Jun
authors.initials: HJ
authors.lastname: Jang
authors.forename: Jaeyoon
authors.initials: J
authors.lastname: Kim
authors.forename: Yong Ryoul
authors.initials: YR
authors.lastname: Yang
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Sanguk
authors.initials: S
authors.lastname: Yun
authors.forename: Girdhari
authors.initials: G
authors.lastname: Rijal
authors.forename: Whaseon
authors.initials: W
authors.lastname: Lee-Kwon
authors.forename: Jeong Kon
authors.initials: JK
authors.lastname: Seo
authors.forename: Yong Song
authors.initials: YS
authors.lastname: Gho
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Ryu
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Hur
authors.forename: Pann-Ghill
authors.initials: PG
authors.lastname: Suh
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*; D015513:Oncogene Proteins / Q000502:physiology*; D010006:Osteoblasts / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology*; D000071617:Protein Deglycase DJ-1; D051381:Rats
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; C484441:PGAP2 protein, human; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1