title: Fibronectin and its fragments increase with degeneration in the human intervertebral disc.
abstract: METHODS
  This laboratory-based experiment correlates fibronectin content of intervertebral disc with a morphologic grade of degeneration.
  
  
  OBJECTIVE
  To correlate the fibronectin content of the anulus fibrosus and nucleus pulposus with a gross morphologic grade of disc degeneration, and to determine the molecular size of the extractable fibronectin.
  
  
  BACKGROUND
  Intervertebral disc degeneration increases with age and can lead to low back pain. Fibronectin helps to organize the extracellular matrix and provides environmental cues by interaction with cell surface integrins. In other tissues, its synthesis is elevated in response to injury. Fibronectin fragments can stimulate cells to produce metalloproteases and cytokines and inhibit matrix synthesis.
  
  
  METHODS
  In this study, 17 anuli fibrosis and 18 nuclei pulposus from 11 spines were graded by Thompson's gross morphologic scale. Fibronectin was sequentially extracted with 4 mol/L guanidine hydrochloride and trypsin, and then quantitated by enzyme-linked immunoassay. The size of extractable fibronectin was determined by Western blot analyses.
  
  
  RESULTS
  The fibronectin content of the disc increased with grade and was significantly elevated between Grades 3 and 4. The percentage of extractable fibronectin varied widely, but it was more extractable from the nucleus. In both the nucleus and anulus, 30% to 40% of the extractable fibronectin existed as fragments. Many of the fragments contained functional heparin or collagen-binding sites.
  
  
  CONCLUSIONS
  Fibronectin is elevated in degenerated discs and frequently present as fragments. Elevated levels of fibronectin suggest that disc cells are responding to the altered environment. Fibronectin fragments resulting from normal or enhanced proteolytic activity could be a mechanism that induces the cell to degrade the matrix further.
authors.affiliation: Department of Orthopaedic Surgery, University of Minnesota, Minneapolis, Minnesota, USA. oegem001@tc.umn.edu
authors.forename: T R
authors.initials: TR
authors.lastname: Oegema
authors.forename: S L
authors.initials: SL
authors.lastname: Johnson
authors.forename: D J
authors.initials: DJ
authors.lastname: Aguiar
authors.forename: J W
authors.initials: JW
authors.lastname: Ogilvie
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D019902:Chondrocytes / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005353:Fibronectins / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007403:Intervertebral Disc / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism
chemical_list: D005353:Fibronectins; D010446:Peptide Fragments