title: Changes in mRNA and protein levels of proteoglycans of the anulus fibrosus and nucleus pulposus during intervertebral disc degeneration.
abstract: METHODS
  This study correlates the mRNA and protein levels of large and small proteoglycans with the morphologic grade of degeneration.
  
  
  OBJECTIVE
  To investigate changes in mRNA and protein levels of aggrecan, versican, biglycan, decorin and fibromodulin in the anulus fibrosus and the nucleus pulposus at different stages of tissue degeneration.
  
  
  BACKGROUND
  Proteoglycans are found in both the anulus fibrosus and nucleus pulposus and contribute to the hydration of the tissue (aggrecan) and the regulation of matrix assembly (small proteoglycans). Changes in their abundance may influence the biochemical and biomechanical properties of the disc and may have an effect on disc function.
  
  
  METHODS
  Thirty-four human lumbar intervertebral discs were graded using Thompson's morphologic scale. The mRNA and protein content of aggrecan, versican, biglycan, decorin and fibromodulin was measured in extracts of anulus fibrosus and nucleus pulposus tissues dissected from these specimens. Protein levels were analyzed by Western blotting, and mRNA levels were semiquantified by reverse transcription polymerase chain reaction.
  
  
  RESULTS
  In the anulus fibrosus, the mRNA and protein content of all proteoglycans was significantly elevated at early stages of degeneration then declined in severely degenerated tissues. In contrast, matrix components in the nucleus pulposus showed a continuous decrease in content with increasing grade of degeneration.
  
  
  CONCLUSIONS
  Cells of the anulus fibrosus and nucleus pulposus react to tissue degeneration differently. Decreased mRNA expression by nucleus pulposus cells and declining protein content of the matrix make the nucleus more vulnerable to degeneration than the anulus. The cells in the anulus fibrosus respond to early degeneration by upregulating biosynthetic processes. However, in heavily degenerated tissues, the decline in the synthesis of aggrecan and the increase in the concentrations of small proteoglycans may be responsible for the failure of the repair processes.
authors.affiliation: Department of Biochemistry, Rush Medical College at Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA. gcaszabo@rush.edu
authors.forename: Gabriella
authors.initials: G
authors.lastname: Cs-Szabo
authors.forename: Deborah
authors.initials: D
authors.lastname: Ragasa-San Juan
authors.forename: Vani
authors.initials: V
authors.lastname: Turumella
authors.forename: Koichi
authors.initials: K
authors.lastname: Masuda
authors.forename: Eugene J-M A
authors.initials: EJ
authors.lastname: Thonar
authors.forename: Howard S
authors.initials: HS
authors.lastname: An
mesh_terms: D053674:Aggrecans; D058578:Biglycan; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D058575:Decorin; D018450:Disease Progression; D016326:Extracellular Matrix Proteins; D005260:Female; D000071235:Fibromodulin; D006801:Humans; D007403:Intervertebral Disc / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D007405:Intervertebral Disc Displacement / Q000378:metabolism* / Q000473:pathology; D037181:Lectins, C-Type; D008161:Lumbosacral Region; D008297:Male; D008875:Middle Aged; D011509:Proteoglycans / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053675:Versicans
chemical_list: D053674:Aggrecans; C546884:BGN protein, human; D058578:Biglycan; D002352:Carrier Proteins; D011508:Chondroitin Sulfate Proteoglycans; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; C000604330:FMOD protein, human; D037181:Lectins, C-Type; D011509:Proteoglycans; D012333:RNA, Messenger; C508322:VCAN protein, human; D000071235:Fibromodulin; D053675:Versicans