title: Nitrite and nitrotyrosine concentrations in articular cartilage, subchondral bone, and trabecular bone of normal juvenile, normal adult, and osteoarthritic adult equine metacarpophalangeal joints.
abstract: OBJECTIVE
  Osteoarthritis (OA) is a chronic debilitating joint disorder in which the importance of inflammation is increasingly recognized. In advanced cases, both the articular cartilage and the underlying bony layers are affected, but the exact sequence of events and their localization in the initial phase of pathogenesis remain uncertain. We measured nitric oxide (NO) end products in tissue layers that constitute the bearing surface of the joint, as possible indicators of physiological and pathological processes.
  
  
  METHODS
  Nitrite as a measure for NO and nitrotyrosine was measured in articular cartilage, subchondral bone, and the underlying trabecular bone of the proximal articular surface of the first phalanx of healthy mature horses (n = 15; age range 5-18 yrs), mature horses affected by OA (n = 15; age range 8-22 yrs), and unaffected juvenile horses (n = 13; age range 6 months-4 yrs). Data were correlated with cartilage damage, as quantified by the Cartilage Degeneration Index.
  
  
  RESULTS
  In all 3 layers the nitrite concentration was higher in OA joints (cartilage, p < 0.001; subchondral and trabecular bone, p < 0.05). The concentration of nitrite was significantly higher in cartilage and subchondral bone of juvenile horses compared with mature horses (p < 0.001). Nitrotyrosine concentrations were significantly higher in subchondral bone of OA horses compared with healthy controls (p < 0.001), but significantly lower in trabecular bone of juvenile horses (p < 0.01).
  
  
  CONCLUSIONS
  The similarities observed over the 3 tissue layers support the concept of the bearing surface of the joint as a functional entity. Nitrite concentration seems to be a good indicator of tissue metabolic activity, but cannot discriminate between physiological (juvenile animals) and pathological (OA cases) processes. The increased nitrotyrosine levels in subchondral bone of OA-affected animals suggest that this layer is important in early or moderate OA, and implies a role of oxidative stress in the development of the disease.
authors.affiliation: Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. markvanderharst@hetnet.nl
authors.forename: Mark
authors.initials: M
authors.lastname: van der Harst
authors.forename: Sarah
authors.initials: S
authors.lastname: Bull
authors.forename: Pieter A J
authors.initials: PA
authors.lastname: Brama
authors.forename: A B
authors.initials: AB
authors.lastname: Barneveld
authors.forename: P René
authors.initials: PR
authors.lastname: van Weeren
authors.forename: Chris
authors.initials: C
authors.lastname: van de Lest
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000737:chemistry / Q000378:metabolism*; D002358:Cartilage, Articular / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D006736:Horses; D008662:Metacarpophalangeal Joint / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D009573:Nitrites / Q000032:analysis / Q000378:metabolism*; D020370:Osteoarthritis, Knee / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism
chemical_list: D009573:Nitrites; C002744:3-nitrotyrosine; D014443:Tyrosine