Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu City, Mie 514-8507, Japan.
J Rheumatol. 2011 Jan;38(1):129-34. doi: 10.3899/jrheum.100637. Epub 2010 Nov 1.
although osteoarthritis (OA) is generally assessed using standard radiographic images in clinical practice, biochemical markers can be used to detect the disease and determine its severity. Osteopontin (OPN) is an extracellular matrix glycoprotein that is a potential inflammatory cytokine. Presence of the thrombin-cleaved form of OPN is well correlated with various inflammatory diseases. We examined whether thrombin-cleaved OPN in synovial fluid (SF) and synovium could be associated with the severity of knee OA.
SF samples were obtained from 139 knees with OA. Thrombin-cleaved OPN product was determined using Western blotting. Levels of thrombin-cleaved and full-length OPN in SF were determined by ELISA. Synovium samples were analyzed by immunohistochemistry using an antibody specific to the thrombin-cleaved form.
western blotting showed the presence of thrombin-cleaved OPN in SF from patients with advanced OA. Concentrations of OPN full-length in OA knees were not statistically different from those in controls (p = 0.134). In contrast, levels of OPN N-half were significantly higher in OA knees than in controls (p = 0.042). Statistically significant correlation was found between thrombin-cleaved OPN and disease severity by Kellgren-Lawrence grade 1, 2, 3, and 4 (R = 0.274, p < 0.001). Immunohistochemistry of the synovium showed stronger reactivity in samples from subjects with advanced OA.
local generation of thrombin-cleaved OPN was increased with greater OA severity.
尽管在临床实践中通常使用标准的放射影像学图像来评估骨关节炎（OA），但生物化学标志物可用于检测疾病并确定其严重程度。骨桥蛋白（OPN）是一种细胞外基质糖蛋白，是一种潜在的炎症细胞因子。凝血酶切割形式的 OPN 的存在与各种炎症性疾病密切相关。我们研究了滑液（SF）和滑膜中凝血酶切割的 OPN 是否与膝骨关节炎的严重程度相关。
从 139 例 OA 膝关节中获得 SF 样本。使用 Western blot 测定凝血酶切割的 OPN 产物。通过 ELISA 测定 SF 中凝血酶切割和全长 OPN 的水平。使用针对凝血酶切割形式的特异性抗体通过免疫组化分析滑膜样本。
Western blot 显示来自晚期 OA 患者的 SF 中存在凝血酶切割的 OPN。OA 膝关节中的 OPN 全长浓度与对照组无统计学差异（p = 0.134）。相比之下，OA 膝关节中的 OPN N-半胱氨酸水平明显高于对照组（p = 0.042）。通过 Kellgren-Lawrence 分级 1、2、3 和 4，发现凝血酶切割的 OPN 与疾病严重程度之间存在统计学显著相关性（R = 0.274，p < 0.001）。对滑膜的免疫组化显示，在 OA 程度较高的样本中反应性更强。
随着 OA 严重程度的增加，局部产生的凝血酶切割的 OPN 增加。
