van der Harst Mark, Bull Sarah, Brama Pieter A J, Barneveld A B, van Weeren P René, van de Lest Chris
Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
J Rheumatol. 2006 Aug;33(8):1662-7.
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.
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.
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).
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.
骨关节炎（OA）是一种慢性致残性关节疾病，炎症在其中的重要性日益得到认可。在晚期病例中，关节软骨和下方的骨层均会受到影响，但发病机制初始阶段的确切事件顺序及其定位仍不确定。我们测量了构成关节承重表面的各组织层中的一氧化氮（NO）终产物，作为生理和病理过程的可能指标。
在健康成熟马匹（n = 15；年龄范围5 - 18岁）、患OA的成熟马匹（n = 15；年龄范围8 - 22岁）以及未受影响的幼年马匹（n = 13；年龄范围6个月 - 4岁）的第一指骨近端关节面的关节软骨、软骨下骨和下方的小梁骨中，测量亚硝酸盐（作为NO的指标）和硝基酪氨酸。数据与通过软骨退变指数量化的软骨损伤相关。
在所有三层中，OA关节中的亚硝酸盐浓度均较高（软骨，p < 0.001；软骨下骨和小梁骨，p < 0.05）。幼年马匹软骨和软骨下骨中的亚硝酸盐浓度显著高于成熟马匹（p < 0.001）。与健康对照组相比，OA马匹软骨下骨中的硝基酪氨酸浓度显著更高（p < 0.001），但幼年马匹小梁骨中的硝基酪氨酸浓度显著更低（p < 0.01）。
在三层组织中观察到的相似性支持将关节承重表面视为一个功能实体的概念。亚硝酸盐浓度似乎是组织代谢活性的良好指标，但无法区分生理过程（幼年动物）和病理过程（OA病例）。OA患病动物软骨下骨中硝基酪氨酸水平的升高表明该层在早期或中度OA中很重要，并暗示氧化应激在疾病发展中起作用。
