title: Roles of neurotrophins in skeletal tissue formation and healing.
abstract: Neurotrophins and their receptors are key molecules that are known to be critical in regulating nervous system development and maintenance and have been recognized to be also involved in regulating tissue formation and healing in skeletal tissues. Studies have shown that neurotrophins and their receptors are widely expressed in skeletal tissues, implicated in chondrogenesis, osteoblastogenesis, and osteoclastogenesis, and are also involved in regulating tissue formation and healing events in skeletal tissue. Increased mRNA expression for neurotrophins NGF, BDNF, NT-3, and NT-4, and their Trk receptors has been observed in injured bone tissues, and NT-3 and its receptor, TrkC, have been identified to have the highest induction at the injury site in a drill-hole injury repair model in both bone and the growth plate. In addition, NT-3 has also recently been shown to be both an osteogenic and angiogenic factor, and this neurotrophin can also enhance expression of the key osteogenic factor, BMP-2, as well as the major angiogenic factor, VEGF, to promote bone formation, vascularization, and healing of the injury site. Further studies, however, are needed to investigate if different neurotrophins have differential roles in skeletal repair, and if NT-3 can be a potential target of intervention for promoting bone fracture healing.
authors.affiliation: Sansom Institute for Health Research and School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Su
authors.affiliation: Sansom Institute for Health Research and School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Xin-Fu
authors.initials: XF
authors.lastname: Zhou
authors.affiliation: Department of Orthopaedic Surgery, Women's and Children's Hospital, North Adelaide, South Australia, Australia.
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Foster
authors.affiliation: Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, Victoria, Australia.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Grills
authors.affiliation: School of Biomedical Sciences, University of Western Australia, Nedlands, Western Australia, Australia.
authors.forename: Jiake
authors.initials: J
authors.lastname: Xu
authors.affiliation: Sansom Institute for Health Research and School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Cory J
authors.identifier: http://orcid.org/0000-0002-8467-2845
authors.initials: CJ
authors.lastname: Xian
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000096:biosynthesis; D016723:Bone Remodeling / Q000502:physiology*; D001842:Bone and Bones / Q000098:blood supply / Q000196:embryology*; D020219:Chondrogenesis / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D020933:Neurotrophin 3; D010006:Osteoblasts / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology*; D020812:Receptor, trkC / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; C000595808:NTF3 protein, human; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D020812:Receptor, trkC
keywords: angiogenesis; bone fracture healing; growth plate repair; neurotrophins; osteogenesis