title: Dynamic loading enhances integrative meniscal repair in the presence of interleukin-1.
abstract: OBJECTIVE
  Meniscal tears are a common knee injury and increased levels of interleukin-1 (IL-1) have been measured in injured and degenerated joints. Studies have shown that IL-1 decreases the shear strength, cell accumulation, and tissue formation in meniscal repair interfaces. While mechanical stress and IL-1 modulate meniscal biosynthesis and degradation, the effects of dynamic loading on meniscal repair are unknown. The purpose of this study was to determine the effects of mechanical compression on meniscal repair under normal and inflammatory conditions.
  
  
  METHODS
  Explants were harvested from porcine medial menisci. To simulate a full-thickness defect, a central core was removed and reinserted. Explants were loaded for 4h/day at 1 Hz and 0%-26% strain for 14 days in the presence of 0 or 100 pg/mL of IL-1. Media were assessed for matrix metalloproteinase (MMP) activity, aggrecanase activity, sulfated glycosaminoglycan (S-GAG) release, and nitric oxide (NO) production. After 14 days, biomechanical testing and histological analyses were performed.
  
  
  RESULTS
  IL-1 increased MMP activity, S-GAG release, and NO production, while decreasing the shear strength and tissue repair in the interface. Dynamic loading antagonized IL-1-mediated inhibition of repair at all strain amplitudes. Neither IL-1 treatment nor strain altered aggrecanase activity. Additionally, strain alone did not alter meniscal healing, except at the highest strain magnitude (26%), a level that enhanced the strength of repair.
  
  
  CONCLUSIONS
  Dynamic loading blocked the catabolic effects of IL-1 on meniscal repair, suggesting that joint loading through physical therapy may be beneficial in promoting healing of meniscal lesions under inflammatory conditions.
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, NC, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: McNulty
authors.forename: B T
authors.initials: BT
authors.lastname: Estes
authors.forename: R E
authors.initials: RE
authors.lastname: Wilusz
authors.forename: J B
authors.initials: JB
authors.lastname: Weinberg
authors.forename: F
authors.initials: F
authors.lastname: Guilak
mesh_terms: D000818:Animals; D010450:Endopeptidases / Q000378:metabolism; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D007718:Knee Injuries / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008592:Menisci, Tibial / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D013314:Stress, Mechanical; D013552:Swine; D000070600:Tibial Meniscus Injuries; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
chemical_list: D006025:Glycosaminoglycans; D007375:Interleukin-1; C013786:A73025; D009569:Nitric Oxide; D010450:Endopeptidases; D020782:Matrix Metalloproteinases; C083641:aggrecanase