Department of Anatomy, Histology and Forensic Medicine, University of Florence, Florence, Italy.
J Rheumatol. 2012 Aug;39(8):1678-86. doi: 10.3899/jrheum.120370. Epub 2012 Jul 1.
Hemarthrosis triggers hemophilic arthropathy, involving the target joints. The histopathogenesis of blood-induced joint damage remains unclear. The triad of receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG; RANK-RANKL-OPG) controls bone turnover. Our aim was to evaluate RANK-RANKL-OPG expression in the synovium of hemophilic patients with severe arthropathy.
Synovial biopsies were obtained from 18 patients with hemophilic arthropathy and 16 with osteoarthritis (OA) who were undergoing total knee replacement and synovectomy. The severity of hemophilic arthropathy was evaluated according to ultrasonography score, the World Federation of Hemophilia (WFH) orthopedic joint scale, and the radiographic Pettersson score. RANK-RANKL-OPG expression was examined by immunohistochemistry and Western blotting. Serum levels of soluble RANKL (sRANKL) and OPG from an extended group of 67 patients with hemophilic arthropathy and 30 healthy controls were measured by ELISA.
The mean ultrasonography, WFH orthopedic joint scale, and Pettersson scores in patients with hemophilic arthropathy indicated severe arthropathy. A decreased expression of OPG was found in hemophilic arthropathy synovium compared with patients with OA. RANK and RANKL immunopositivity was strong in the lining and sublining layers in hemophilic arthropathy synovial tissue. Western blotting confirmed the immunohistological findings. Serum levels of sRANKL and OPG in patients with hemophilia were lower than in healthy controls.
In hemophilic arthropathy, the synovium highly expressed RANK and RANKL, whereas OPG immunopositivity decreased, suggesting an osteoclastic activation. Low tissue expression of OPG paralleled the serum levels of this protein and the severity of hemophilic arthropathy assessed by ultrasonography, Pettersson, and WFH orthopedic joint scale scores.
关节出血会引发血友病性关节病，累及靶关节。血液引起的关节损伤的组织病理学发病机制尚不清楚。核因子-κB 受体激活剂（RANK）、RANK 配体（RANKL）和护骨素（OPG；RANK-RANKL-OPG）三连环控制着骨骼的新陈代谢。我们的目的是评估患有严重关节病的血友病患者的滑膜中 RANK-RANKL-OPG 的表达。
从 18 名患有血友病性关节病和 16 名患有骨关节炎（OA）的患者中获取滑膜活检样本，这些患者正在接受全膝关节置换和滑膜切除术。根据超声评分、世界血友病联盟（WFH）矫形关节评分和 Pettersson 放射评分评估血友病性关节病的严重程度。通过免疫组织化学和 Western blot 检测 RANK-RANKL-OPG 的表达。通过 ELISA 检测来自扩展组的 67 名血友病性关节病患者和 30 名健康对照者的血清可溶性 RANKL（sRANKL）和 OPG 水平。
血友病性关节病患者的平均超声评分、WFH 矫形关节评分和 Pettersson 评分表明存在严重的关节病。与 OA 患者相比，血友病性关节病滑膜中的 OPG 表达减少。血友病性关节病滑膜组织的衬里和亚衬里层中 RANK 和 RANKL 的免疫阳性反应较强。Western blot 证实了免疫组织化学的发现。血友病患者的血清 sRANKL 和 OPG 水平低于健康对照组。
在血友病性关节病中，滑膜高表达 RANK 和 RANKL，而 OPG 的免疫阳性反应减少，表明破骨细胞被激活。OPG 的组织表达水平较低与该蛋白的血清水平以及超声评分、Pettersson 和 WFH 矫形关节评分评估的血友病性关节病的严重程度相平行。
