title: The effect of dynamic mechanical compression on nitric oxide production in the meniscus.
abstract: OBJECTIVE
  The menisci play an important role in the biomechanics of the knee, and loss of meniscal function has been associated with progressive degenerative changes of the joint in rheumatoid arthritis as well as in osteoarthritis. However, little is known about the underlying mechanisms that link meniscal injury or degeneration to arthritis. Meniscal fibrochondrocytes respond to environmental mediators such as growth factors and cytokines, but the influence of mechanical stress on their metabolic activity is not well understood. Nitric oxide (NO) is believed to play a role in mechanical signal transduction, and there is also significant evidence of its role in cartilage and meniscus degeneration. The goal of this study was to determine if meniscal fibrochondrocytes respond to mechanical stress by increasing NO production in vitro.
  
  
  METHODS
  Explants of lateral and medial porcine menisci were dynamically compressed in a precisely controlled manner, and NO production, nitric oxide synthase antigen expression and cell viability were measured. The relative responses of the meniscal surface and deep layers to dynamic compression were also investigated separately.
  
  
  RESULTS
  Meniscal NO production was significantly (P< 0.01) increased by dynamic compression in both the medial and lateral menisci. Dynamically compressed menisci contained inducible nitric oxide synthase antigen, while uncompressed menisci did not. Significant (P< 0.05) zonal differences were observed in basal and compression-induced NO production.
  
  
  CONCLUSIONS
  Our findings provide direct evidence that dynamic mechanical stress influences the biological activity of meniscal cells. These results suggest that NO production in vivo may be in part regulated by mechanical stress acting upon the menisci. Since NO affects matrix metabolism in various intraarticular tissues, alterations in the distribution and magnitude of stress in the menisci may have important metabolic as well as biomechanical consequences on joint physiology and function.
authors.affiliation: Department of Surgery, Division of Orthopaedic Surgery, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: C
authors.initials: C
authors.lastname: Fink
authors.forename: B
authors.initials: B
authors.lastname: Fermor
authors.forename: J B
authors.initials: JB
authors.lastname: Weinberg
authors.forename: D S
authors.initials: DS
authors.lastname: Pisetsky
authors.forename: M A
authors.initials: MA
authors.lastname: Misukonis
authors.forename: F
authors.initials: F
authors.lastname: Guilak
mesh_terms: D000818:Animals; D000941:Antigens / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D002470:Cell Survival; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006614:Hindlimb; D008592:Menisci, Tibial / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000276:immunology; D052247:Nitric Oxide Synthase Type II; D020370:Osteoarthritis, Knee / Q000378:metabolism; D013314:Stress, Mechanical; D013552:Swine
chemical_list: D000941:Antigens; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II