title: In vitro inhibition of compression-induced catabolic gene expression in meniscal explants following treatment with IL-1 receptor antagonist.
abstract: BACKGROUND
  Damage to the knee meniscus may result in tears that are difficult or unable to heal, and are often treated by partial removal of the damaged tissue. In vitro, 20% dynamic compressive strains on meniscal tissue explants have resulted in an increase in the release of sulfated glycosaminoglycans (GAG) and nitric oxide (NO) from the tissue explants and increased expression of matrix metalloproteinases (MMP) and interleukin-1α (IL-1α). The objective of this study was to explore the efficacy of IL-1 blockade on the expression of a wide range of genes, as well as NO and GAG release, following dynamic compression of porcine meniscal explants.
  
  
  METHODS
  Explants were dynamically compressed for 2 h at 1 Hz to 0, 10, or 20% strain with and without a pre-treatment of 500 ng/ml interleukin-1 receptor antagonist (IL-1RA). Relative changes in gene expression of IL-1α, MMP-1, -3, -13, A Disintegrin and Metalloproteinase with ThromboSpondin 4 (ADAMTS-4), ADAMTS-5, iNOS, aggrecan, and COX-2, as well as changes in NO and GAG release, were measured with standard biochemical assays.
  
  
  RESULTS
  Expression of IL-1α, MMP-3, MMP-13, and ADAMTS-4 in superficial explants was significantly downregulated at 20% dynamic strain compared to 10% strain following treatment with IL-1RA. GAG and NO release were not significantly influenced by IL-1RA treatment.
  
  
  CONCLUSIONS
  Treatment of meniscal explants with IL-1RA inhibited the expression of many catabolic genes following a single bout of high dynamic strain. IL-1RA may therefore be a potential therapy option during the acute phase of meniscal tear or meniscectomy treatment.
authors.affiliation: Department of Mechanical Engineering-Engineering Mechanics, Michigan Technological University, 815 R.L. Smith Building, 1400 Townsend Dr, Houghton, MI 49931, USA.
authors.forename: Megan Leigh
authors.initials: ML
authors.lastname: Killian
authors.forename: Barbara
authors.initials: B
authors.lastname: Zielinska
authors.forename: Tumul
authors.initials: T
authors.lastname: Gupta
authors.forename: Tammy Lynn
authors.initials: TL
authors.lastname: Haut Donahue
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology; D002373:Cyclic AMP Receptor Protein / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000235:genetics*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology*; D007718:Knee Injuries / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008592:Menisci, Tibial / Q000378:metabolism* / Q000473:pathology; D012313:RNA / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012421:Rupture; D013552:Swine; D000070600:Tibial Meniscus Injuries
chemical_list: D018501:Antirheumatic Agents; D002373:Cyclic AMP Receptor Protein; D053590:Interleukin 1 Receptor Antagonist Protein; D012313:RNA