title: Brain-derived neurotrophic factor and its receptor in the human and the sand rat intervertebral disc.
abstract: BACKGROUND
  Brain-derived neurotrophic factor (BDNF) was first identified in the intervertebral disc (IVD) when its molecular upregulation was observed in sections of nucleus pulposus cultured under conditions of increased osmolarity. BDNF is now known to be involved in a number of biologic functions, including regulation of differentiation/survival of sensory neurons, regulation of nociceptive function and central pain modulation, and modulation of inflammatory pain hypersensitivity. In addition, more recent investigations show that BDNF can induce the recruitment of endothelial cells and the formation of vascular structures. The objectives of the present study were to use immunocytochemistry to determine the distribution of BDNF and its receptor (BDNF-tropomyosine receptor kinase B) in the human IVD, and to test for gene expression of BDNF and its receptor in cultured human annulus fibrosus cells.
  
  
  METHODS
  We studied immunohistochemical localization of BDNF and its receptor in the human annulus, quantified the percentage of outer annulus and inner annulus cells and nucleus cells positive for BDNF immunolocalization, and studied the gene expression of BDNF and its receptor using microarray analysis.
  
  
  RESULTS
  The percentage (mean +/- standard error of the mean) of cells positive for BDNF localization was significantly greater in the outer annulus (32.3 +/- 2.7%, n = 22) compared with either the inner annulus (8.1 +/- 1.5%, n = 6) or the nucleus (10.4 +/- 2.8%, n = 3) (P < 0.0001). BDNF-receptor immunolocalization showed a pattern similar to that of BDNF, but was not quantitatively assessed. BDNF gene expression levels from cultured annulus cells showed a significant positive correlation with increasing levels of IVD degeneration (P = 0.011).
  
  
  CONCLUSIONS
  These findings provide data on the presence of BDNF and its receptor in the human IVD at the translational level, and on the expression of BDNF and its receptor by cultured human annulus cells. Our findings point to the need for further studies to define the role of BDNF in the human IVD and to investigate regulatory events within the disc that control the expression of BDNF and its receptor.
authors.affiliation: Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte, NC 28232, USA. helen.gruber@carolinashealthcare.org
authors.forename: Helen E
authors.initials: HE
authors.lastname: Gruber
authors.forename: Jane A
authors.initials: JA
authors.lastname: Ingram
authors.forename: Gretchen
authors.initials: G
authors.lastname: Hoelscher
authors.forename: Natalia
authors.initials: N
authors.lastname: Zinchenko
authors.forename: H James
authors.initials: HJ
authors.lastname: Norton
authors.forename: Edward N
authors.initials: EN
authors.lastname: Hanley
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D005849:Gerbillinae; D006801:Humans; D007403:Intervertebral Disc / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D051381:Rats; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020813:Receptor, trkB