title: The involvement of oxidants and NF-κB in cytokine-induced MMP-9 synthesis by bone marrow-derived osteoprogenitor cells.
abstract: OBJECTIVE
  The activity of immune cells affects the balance between bone mineralization and resorption carried out by the opposing actions of osteoblasts and osteoclasts, respectively. This study was aimed at determining the possible interaction between inflammatory conditions and collagen type I degrading MMP (mainly MMP-2 and MMP-9) synthesis and secretion in rat osteoprogenitors.
  
  
  METHODS
  The study was performed using primary rat bone marrow-derived osteoprogenitors during their advanced osteogenesis. Biochemical, immunohistochemical, and molecular biology techniques were used to investigate the influence of pro-inflammatory cytokines on MMP-2 and MMP-9 synthesis and secretion in osteoprogenitors.
  
  
  RESULTS
  Results indicated that both synthesis and secretion of MMPs (MMP-1, -2, -8, -9, and -13) were significantly induced after pro-inflammatory cytokine treatments, except MMP-2, whose levels remained unchanged. NF-κB (nuclear factor kappa-light chain enhancer of activated B cells) inhibition assays showed that induced MMP-9 secretion by inflammatory cytokines was mediated by activation of NF-κB via the classical pathway and that oxidants play a significant role in this signal transduction pathway. In contrast, no such effect was observed for synthesis of MMP-2.
  
  
  CONCLUSIONS
  These results indicate the possibility that inflammatory processes may trigger osteoblasts to absorb bone by secreting elevated levels of MMPs capable of degrading collagen type I, especially MMP-9 which is upregulated due to increased NF-κB transcription activity.
authors.affiliation: Department of Anatomy and Cell Biology, Faculty of Medicine, Technion, P.O. Box 9649, 31096 Haifa, Israel.
authors.forename: Dror
authors.initials: D
authors.lastname: Ben-David
authors.forename: Erella
authors.initials: E
authors.lastname: Livne
authors.forename: Abraham Z
authors.initials: AZ
authors.lastname: Reznick
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D053582:Interleukin-1alpha / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D024042:Collagen Type I; D020672:I-kappa B Proteins; D053582:Interleukin-1alpha; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D002084:Butylated Hydroxytoluene; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; D000111:Acetylcysteine