title: Type IX collagen neo-deposition in degenerative discs of surgical patients whether genotyped plus or minus for COL9 risk alleles.
abstract: METHODS
  Immunohistochemical analysis of type IX collagen in disc tissue from spinal fusion patients.
  
  
  OBJECTIVE
  To determine if collagen IX can be detected in adult disc tissue removed at spinal fusion surgery from patients either with or without degeneration-associated tryptophan single nucleotide polymorphisms (SNPs) and whether the distribution is associated either with severity of degeneration or incidence of a collagen IX SNP genotype.
  
  
  BACKGROUND
  Genetic factors are strongly associated with risk of development and/or progression of disc degeneration. Two SNPs that introduce tryptophan polymorphisms in COL9A2 and COL9A3 are independently linked to an increased risk of lumbar disc disease. Although tryptophan variants are associated with accelerated degeneration, it is not known if collagen IX can be detected in adult disc tissue.
  
  
  METHODS
  We selected age-matched disc samples from five clinical groups: fracture with Trp(-) (six cases), herniation (six cases), degeneration (five cases), spondylolisthesis with Trp(-) (eight cases), and spondylolisthesis/herniation/fracture with Trp(+) (six cases of Trp3 allele and one case of Trp2 allele). Using hematoxylin and eosin staining and immunohistochemical staining (collagens IX and IIA), 78 sections from 32 patients were analyzed. Selected disc tissues were assayed biochemically for collagen IX.
  
  
  RESULTS
  Focal deposition of collagen IX was observed in regions of adult human disc tissue from spines showing degenerative changes in patients whether or not they were positive for a tryptophan SNP. However, in nondegenerative control disc tissue from fracture cases, little or no collagen IX was detected. The latter finding was confirmed by direct biochemical analyses for collagen IX in pooled samples of normal adult human annulus fibrosus or nucleus pulposus.
  
  
  CONCLUSIONS
  During growth and maturation of the disc, collagen IX is presumably removed completely during matrix remodeling so that the protein is absent from normal adult annulus and nucleus but can reappear at sites of degeneration presumably as part of a repair response to mechanical injury.
authors.affiliation: Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jiann-Jiu
authors.initials: JJ
authors.lastname: Wu
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Weis
authors.forename: Sohail K
authors.initials: SK
authors.lastname: Mirza
authors.forename: David R
authors.initials: DR
authors.lastname: Eyre
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D015153:Blotting, Western; D024081:Collagen Type IX / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D055959:Intervertebral Disc Degeneration / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D007405:Intervertebral Disc Displacement / Q000235:genetics / Q000378:metabolism / Q000601:surgery; D008159:Lumbar Vertebrae / Q000378:metabolism / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D016103:Spinal Fractures / Q000235:genetics / Q000378:metabolism / Q000601:surgery; D013130:Spinal Stenosis / Q000235:genetics / Q000378:metabolism / Q000601:surgery; D013168:Spondylolisthesis / Q000235:genetics / Q000378:metabolism; D014364:Tryptophan / Q000235:genetics; D055815:Young Adult
chemical_list: C120282:COL9A2 protein, human; C120768:COL9A3 protein, human; D024081:Collagen Type IX; D014364:Tryptophan