BDNF and its TrkB receptor in human fracture healing

• Published in: Annals of anatomy Vol. 196; no. 5; pp. 286 - 295
• Main Authors: Kilian, Olaf, Hartmann, Sonja, Dongowski, Nicole, Karnati, Srikanth, Baumgart-Vogt, Eveline, Härtel, Frauke V., Noll, Thomas, Schnettler, Reinhard, Lips, Katrin Susanne
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.09.2014
• Subjects: Adult; Aged; Angiogenesis; Blood vessel; Bone; Bone and Bones - metabolism; Bone and Bones - physiology; Bone Development - physiology; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Brain-Derived Neurotrophic Factor - physiology; Cell Line; Female; Fracture Healing - physiology; Humans; Ilium - physiology; Male; Middle Aged; Neurotrophin; Osteoblast; Osteoblasts - physiology; Receptor, trkB - metabolism; Receptor, trkB - physiology; Tropomyosin-related kinases; Young Adult; Neurotrophin; Angiogenesis; Brain-derived neurotrophic factor; Tropomyosin-related kinases; Blood vessel; Osteoblast; Bone
• ISSN: 0940-9602; 1618-0402
• DOI: 10.1016/j.aanat.2014.06.001

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.