Vandooren Bernard, Cantaert Tineke, Noordenbos Troy, Tak Paul P, Baeten Dominique
Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.
Arthritis Rheum. 2008 Mar;58(3):718-29. doi: 10.1002/art.23290.
Spondylarthritis (SpA) and rheumatoid arthritis (RA) have different patterns of bone damage, with more pronounced bone erosions in RA. The RANK/RANKL/osteoprotegerin (OPG) system plays a central role in bone resorption by promoting the maturation and activation of osteoclasts. To assess the potential role of this system in the distinct bone phenotype, we studied the synovial expression of these mediators in SpA and RA peripheral synovitis.
Synovial biopsy specimens were obtained from the actively inflamed peripheral joints of 35 patients with SpA and 19 patients with RA. Paired synovial biopsy samples were obtained from 24 patients with SpA after tumor necrosis factor alpha (TNFalpha) blockade. Synovial tissue sections were immunostained for RANKL, OPG, RANK, and TRAP and assessed by semiquantitative scoring and digital image analysis.
After extensive validation of the reactivity and specificity of the antibodies, we demonstrated the abundant expression of RANKL and OPG in SpA synovitis. RANKL was expressed by both fibroblast-like synoviocytes and sublining T lymphocytes. RANK-positive osteoclast precursors but no mature TRAP-positive osteoclasts were present in the inflamed tissue. The expression of these mediators was not different between patients with nonpsoriatic SpA, patients with psoriatic SpA, and patients with RA, was not related to the degree of systemic or local inflammation, and was not significantly modulated by highly effective treatment with TNFalpha blockers. Only the subset of patients with the best systemic response to TNFalpha blockade had decreased RANKL expression in the intimal lining layer.
The relative protection against bone erosions in SpA cannot be explained by qualitative or quantitative differences in the synovial expression of RANKL, OPG, and RANK. The abundant expression of these factors in SpA peripheral synovitis is largely disconnected from systemic and local inflammation.
脊柱关节炎（SpA）和类风湿关节炎（RA）具有不同的骨损伤模式，RA中的骨侵蚀更为明显。核因子κB受体活化因子（RANK）/核因子κB受体活化因子配体（RANKL）/骨保护素（OPG）系统通过促进破骨细胞的成熟和活化在骨吸收中起核心作用。为了评估该系统在不同骨表型中的潜在作用，我们研究了这些介质在SpA和RA外周滑膜炎中的滑膜表达。
从35例SpA患者和19例RA患者的活动性炎症外周关节获取滑膜活检标本。从24例接受肿瘤坏死因子α（TNFα）阻断治疗后的SpA患者中获取配对的滑膜活检样本。对滑膜组织切片进行RANKL、OPG、RANK和抗酒石酸酸性磷酸酶（TRAP）免疫染色，并通过半定量评分和数字图像分析进行评估。
在广泛验证抗体的反应性和特异性后，我们证明了RANKL和OPG在SpA滑膜炎中大量表达。RANKL由成纤维细胞样滑膜细胞和衬里下T淋巴细胞表达。炎症组织中存在RANK阳性破骨细胞前体，但无成熟的TRAP阳性破骨细胞。这些介质的表达在非银屑病性SpA患者、银屑病性SpA患者和RA患者之间无差异，与全身或局部炎症程度无关，且未被TNFα阻滞剂的高效治疗显著调节。只有对TNFα阻断治疗全身反应最佳的患者亚组在内膜衬里层中RANKL表达降低。
SpA对骨侵蚀的相对保护作用不能通过RANKL、OPG和RANK滑膜表达的定性或定量差异来解释。这些因子在SpA外周滑膜炎中的大量表达在很大程度上与全身和局部炎症无关。
