Engdahl Cecilia, Lindholm Catharina, Stubelius Alexandra, Ohlsson Claes, Carlsten Hans, Lagerquist Marie K
University of Gothenburg, Gothenburg, Sweden.
Arthritis Rheum. 2013 Nov;65(11):2857-65. doi: 10.1002/art.38114.
Bone loss in arthritis is a complex process characterized by bone erosions and periarticular and generalized bone loss. The antigen-induced arthritis (AIA) model is mainly used to study synovitis and joint destruction, including bone erosions; however, periarticular bone loss has been less extensively investigated. The objectives of this study were to characterize and establish AIA as a model for periarticular bone loss, and to determine the importance of NADPH oxidase 2 (NOX-2)-derived reactive oxygen species (ROS) in periarticular bone loss.
Arthritis was induced in mice by local injection of antigen in one knee; the other knee was used as a nonarthritis control. At study termination, the knees were collected for histologic assessment. Periarticular bone mineral density (BMD) was investigated by peripheral quantitative computed tomography. Flow cytometric analyses were performed using synovial and bone marrow cells.
AIA resulted in decreased periarticular trabecular BMD and increased frequencies of preosteoclasts, neutrophils, and monocytes in the arthritic synovial tissue. Arthritis induction resulted in an increased capability to produce ROS. However, induction of arthritis in Ncf1 / mice, which lack NOX-2-derived ROS, and control mice resulted in similar reductions in periarticular trabecular BMD.
The initiation of AIA resulted in periarticular bone loss associated with local effects on inflammatory cells and osteoclasts. Furthermore, based on our observations using this model, we conclude that NOX-2-derived ROS production is not essential for inflammation-mediated periarticular bone loss. Thus, AIA can be used as a model to investigate the pathogenesis of local inflammation-mediated bone loss.
关节炎中的骨质流失是一个复杂的过程，其特征为骨侵蚀以及关节周围和全身性骨质流失。抗原诱导性关节炎（AIA）模型主要用于研究滑膜炎和关节破坏，包括骨侵蚀；然而，关节周围骨质流失的研究较少。本研究的目的是表征并将AIA确立为关节周围骨质流失的模型，并确定NADPH氧化酶2（NOX-2）衍生的活性氧（ROS）在关节周围骨质流失中的重要性。
通过在一侧膝关节局部注射抗原诱导小鼠发生关节炎；另一侧膝关节用作非关节炎对照。在研究结束时，收集膝关节进行组织学评估。通过外周定量计算机断层扫描研究关节周围骨矿物质密度（BMD）。使用滑膜和骨髓细胞进行流式细胞术分析。
AIA导致关节周围小梁骨密度降低，关节炎滑膜组织中破骨细胞前体细胞、中性粒细胞和单核细胞的频率增加。关节炎诱导导致产生ROS的能力增强。然而，在缺乏NOX-2衍生ROS的Ncf1 /小鼠和对照小鼠中诱导关节炎导致关节周围小梁骨密度出现类似程度的降低。
AIA的起始导致关节周围骨质流失，这与对炎症细胞和破骨细胞的局部影响有关。此外，基于我们使用该模型的观察结果，我们得出结论，NOX-2衍生的ROS产生对于炎症介导的关节周围骨质流失并非必不可少。因此，AIA可作为研究局部炎症介导的骨质流失发病机制的模型。
