title: Interleukin-1, tumor necrosis factor-alpha, and transforming growth factor-beta 1 and integrative meniscal repair: influences on meniscal cell proliferation and migration.
abstract: BACKGROUND
  Interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) are up-regulated in injured and osteoarthritic knee joints. IL-1 and TNF-α inhibit integrative meniscal repair; however, the mechanisms by which this inhibition occurs are not fully understood. Transforming growth factor-β1 (TGF-β1) increases meniscal cell proliferation and accumulation, and enhances integrative meniscal repair. An improved understanding of the mechanisms modulating meniscal cell proliferation and migration will help to improve approaches for enhancing intrinsic or tissue-engineered repair of the meniscus. The goal of this study was to examine the hypothesis that IL-1 and TNF-α suppress, while TGF-β1 enhances, cellular proliferation and migration in cell and tissue models of meniscal repair.
  
  
  METHODS
  A micro-wound assay was used to assess meniscal cell migration and proliferation in response to the following treatments for 0, 24, or 48 hours: 0 to 10 ng/mL IL-1, TNF-α, or TGF-β1, in the presence or absence of 10% serum. Proliferated and total cells were fluorescently labeled and imaged using confocal laser scanning microscopy and the number of proliferated, migrated, and total cells was determined in the micro-wound and edges of each image. Meniscal cell proliferation was also assessed throughout meniscal repair model explants treated with 0 or 10 ng/mL IL-1, TNF-α, or TGF-β1 for 14 days. At the end of the culture period, biomechanical testing and histological analyses were also performed. Statistical differences were assessed using an ANOVA and Newman-Keuls post hoc test.
  
  
  RESULTS
  IL-1 and TNF-α decreased cell proliferation in both cell and tissue models of meniscal repair. In the presence of serum, TGF-β1 increased outer zone cell proliferation in the micro-wound and in the cross section of meniscal repair model explants. Both IL-1 and TNF-α decreased the integrative shear strength of repair and extracellular matrix deposition in the meniscal repair model system, while TGF-β1 had no effect on either measure.
  
  
  CONCLUSIONS
  Meniscal cell proliferation in vivo may be diminished following joint injury due to the up-regulation of inflammatory cytokines, thereby limiting native cellular repair of meniscal lesions. Therefore, therapies that can promote meniscal cell proliferation have promise to enhance meniscal repair and improve tissue engineering strategies.
authors.affiliation: Department of Orthopaedic Surgery, Duke University Medical Center, DUMC Box 3093, Durham, NC 27710, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Riera
authors.forename: Nicole E
authors.initials: NE
authors.lastname: Rothfusz
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Wilusz
authors.forename: J B
authors.initials: JB
authors.lastname: Weinberg
authors.forename: Farshid
authors.initials: F
authors.lastname: Guilak
authors.forename: Amy L
authors.initials: AL
authors.lastname: McNulty
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D007375:Interleukin-1 / Q000494:pharmacology*; D008592:Menisci, Tibial / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D018613:Microscopy, Confocal; D013552:Swine; D046509:Tissue Culture Techniques; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D007375:Interleukin-1; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha
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