title: Nitric oxide production and apoptosis in cells of the meniscus during experimental osteoarthritis.
abstract: OBJECTIVE
  To examine the pathologic changes in meniscus tissue during experimental osteoarthritis (OA) and to determine the relationship between nitric oxide (NO) synthesis, apoptosis, and meniscus degradation.
  
  
  METHODS
  OA was induced in rabbits by anterior cruciate ligament (ACL) transection. Knees were harvested after 9 weeks and assessed for OA severity. Menisci were subjected to histologic, immunohistochemical, and electron microscopic analyses for the presence of nitrotyrosine and apoptosis. Menisci were also cultured for analysis of NO production.
  
  
  RESULTS
  All menisci from joints with ACL transection demonstrated degenerative changes. A high number of apoptotic cells was present in the medial part of menisci, which contains chondrocytic cells. Menisci from nonoperated contralateral knees contained only small numbers of cells in apoptosis. Conditioned media from meniscus cultures contained similarly elevated levels of nitrite as cartilage cultures from the same arthritic knees. Nitrotyrosine immunoreactivity, an indicator of in vivo NO production, was prominent in menisci from knees with ACL transection. In addition, menisci from normal knees produced high levels of NO in response to in vitro stimulation with interleukin-1beta or lipopolysaccharide.
  
  
  CONCLUSIONS
  These observations suggest that pathologic changes in menisci are a regular feature of experimentally induced OA and are associated with NO production and meniscus cell apoptosis.
authors.affiliation: The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: S
authors.initials: S
authors.lastname: Hashimoto
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: R L
authors.initials: RL
authors.lastname: Ochs
authors.forename: R D
authors.initials: RD
authors.lastname: Coutts
authors.forename: D
authors.initials: D
authors.lastname: Amiel
authors.forename: M
authors.initials: M
authors.lastname: Lotz
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D008592:Menisci, Tibial / Q000378:metabolism* / Q000473:pathology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology*; D011817:Rabbits; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
chemical_list: D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine