title: Human MMP28 expression is unresponsive to inflammatory stimuli and does not correlate to the grade of intervertebral disc degeneration.
abstract: BACKGROUND
  MMP28 (epilysin) is a recently discovered member of the MMP (matrix metalloproteinase) family that is, amongst others, expressed in osteoarthritic cartilage and intervertebral disc (IVD) tissue. In this study the hypothesis that increased expression of MMP28 correlates with higher grades of degeneration and is stimulated by the presence of proinflammatory molecules was tested. Gene expression levels of MMP28 were investigated in traumatic and degenerative human IVD tissue and correlated to the type of disease and the degree of degeneration (Thompson grade). Quantification of MMP28 gene expression in human IVD tissue or in isolated cells after stimulation with the inflammatory mediators lipopolysaccharide (LPS), interleukin (IL)-1β, tumor necrosis factor (TNF)-α or the histondeacetylase inhibitor trichostatin A was performed by real-time RT PCR.
  
  
  RESULTS
  While MMP28 expression was increased in individual cases with trauma or disc degeneration, there was no significant correlation between the grade of disease and MMP28 expression. Stimulation with LPS, IL-1β, TNF-α or trichostatin A did not alter MMP28 gene expression at any investigated time point or any concentration.
  
  
  CONCLUSIONS
  Our results demonstrate that gene expression of MMP28 in the IVD is not regulated by inflammatory mechanisms, is donor-dependent and cannot be positively or negatively linked to the grade of degeneration and only weakly to the occurrence of trauma. New hypotheses and future studies are needed to find the role of MMP28 in the intervertebral disc.
authors.affiliation: Spine Research Group, Competence Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Marina
authors.initials: M
authors.lastname: Klawitter
authors.forename: Lilian
authors.initials: L
authors.lastname: Quero
authors.forename: Alessando
authors.initials: A
authors.lastname: Bertolo
authors.forename: Marco
authors.initials: M
authors.lastname: Mehr
authors.forename: Jivko
authors.initials: J
authors.lastname: Stoyanov
authors.forename: Andreas G
authors.initials: AG
authors.lastname: Nerlich
authors.forename: Juergen
authors.initials: J
authors.lastname: Klasen
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Aebli
authors.forename: Norbert
authors.initials: N
authors.lastname: Boos
authors.forename: Karin
authors.initials: K
authors.lastname: Wuertz
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology; D055959:Intervertebral Disc Degeneration / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D053505:Matrix Metalloproteinases, Secreted / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D013124:Spinal Injuries / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D006877:Hydroxamic Acids; D018836:Inflammation Mediators; D007375:Interleukin-1; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C012589:trichostatin A; C424663:MMP28 protein, human; D053505:Matrix Metalloproteinases, Secreted