title: BDNF and its TrkB receptor in human fracture healing.
abstract: Fracture healing is a physiological process of repair which proceeds in stages, each characterized by a different predominant tissue in the fracture gap. Matrix reorganization is regulated by cytokines and growth factors. Neurotrophins and their receptors might be of importance to osteoblasts and endothelial cells during fracture healing. The aim of this study was to examine the presence of brain-derived neurotrophic factor (BDNF) and its tropomyosin-related kinase B receptor (TrkB) during human fracture healing. BDNF and TrkB were investigated in samples from human fracture gaps and cultured cells using RT-PCR, Western blot, and immunohistochemistry. Endothelial cells and osteoblastic cell lines demonstrated a cytoplasmic staining pattern of BDNF and TrkB in vitro. At the mRNA level, BDNF and TrkB were expressed in the initial and osteoid formation phase of human fracture healing. In the granulation tissue of fracture gap, both proteins--BDNF and TrkB--are concentrated in endothelial and osteoblastic cells at the margins of woven bone suggesting their involvement in the formation of new vessels. There was no evidence of BDNF or TrkB during fracture healing in chondrocytes of human enchondral tissue. Furthermore, BDNF is absent in mature bone. Taken together, BDNF and TrkB are involved in vessel formation and osteogenic processes during human fracture healing. The detection of BDNF and its TrkB receptor during various stages of the bone formation process in human fracture gap tissue were shown for the first time. The current study reveals that both proteins are up-regulated in human osteoblasts and endothelial cells in fracture healing.
authors.affiliation: Laboratory of Experimental Trauma Surgery, University of Giessen, Kerkraderstr. 9, 35392 Giessen, Germany; Department of Orthopedics and Trauma, Zentralklinik Bad Berka, Robert-Koch-Allee 9, 99437 Bad Berka, Germany. Electronic address: olaf.kilian@gmx.de.
authors.forename: Olaf
authors.initials: O
authors.lastname: Kilian
authors.affiliation: Laboratory of Experimental Trauma Surgery, University of Giessen, Kerkraderstr. 9, 35392 Giessen, Germany. Electronic address: Sonja.hartmann@chiru.med.uni-giessen.de.
authors.forename: Sonja
authors.initials: S
authors.lastname: Hartmann
authors.affiliation: Department of Trauma Surgery, Asklepios Klinik Lich, Goethestr. 4, 35423 Lich, Germany. Electronic address: Nicole.dongowski@chiru.med.uni-giessen.de.
authors.forename: Nicole
authors.initials: N
authors.lastname: Dongowski
authors.affiliation: Institute for Anatomy and Cell Biology II, Division of Medical Cell Biology, University of Giessen, Aulweg 123, 35392 Giessen, Germany. Electronic address: Srikanth.karnati@anatomie.med.uni-giessen.de.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Karnati
authors.affiliation: Institute for Anatomy and Cell Biology II, Division of Medical Cell Biology, University of Giessen, Aulweg 123, 35392 Giessen, Germany. Electronic address: Eveline.baumgart-vogt@anatomie.med.uni-giessen.de.
authors.forename: Eveline
authors.initials: E
authors.lastname: Baumgart-Vogt
authors.affiliation: Institute of Physiology, University of Giessen, Aulweg 129, 35392 Giessen, Germany. Electronic address: Frauke.v.haertel@physiologie.med.uni-giesssen.de.
authors.forename: Frauke V
authors.initials: FV
authors.lastname: Härtel
authors.affiliation: Institute of Physiology, University of Giessen, Aulweg 129, 35392 Giessen, Germany. Electronic address: Thomas.noll@physiologie.med.uni-giessen.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Noll
authors.affiliation: Laboratory of Experimental Trauma Surgery, University of Giessen, Kerkraderstr. 9, 35392 Giessen, Germany; Department of Trauma Surgery, University of Giessen, Rudolf-Buchheim-Str. 7, 35385 Giessen, Germany. Electronic address: Reinhard.schnettler@chiru.med.uni-giessen.de.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schnettler
authors.affiliation: Laboratory of Experimental Trauma Surgery, University of Giessen, Kerkraderstr. 9, 35392 Giessen, Germany. Electronic address: Katrin.s.lips@chiru.med.uni-giessen.de.
authors.forename: Katrin Susanne
authors.initials: KS
authors.lastname: Lips
mesh_terms: D000328:Adult; D000368:Aged; D001846:Bone Development / Q000502:physiology; D001842:Bone and Bones / Q000378:metabolism / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D005260:Female; D017102:Fracture Healing / Q000502:physiology*; D006801:Humans; D007085:Ilium / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000502:physiology; D020813:Receptor, trkB / Q000378:metabolism / Q000502:physiology*; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020813:Receptor, trkB
keywords: Angiogenesis; Blood vessel; Bone; Brain-derived neurotrophic factor; Neurotrophin; Osteoblast; Tropomyosin-related kinases