Department of Rheumatology, Aarhus University Hospital, Nørrebrogade 44, 8000 Aarhus C, Denmark.
Rheumatol Int. 2013 May;33(5):1127-33. doi: 10.1007/s00296-012-2500-7. Epub 2012 Sep 5.
The aim was to further characterize the SKG model of rheumatoid arthritis (RA) and its potential for studying intervention treatments, with special focus on bone targeting therapies. Three individual studies were conducted, using a total of 71 SKG mice, comparing arthritis induction with mannan versus zymosan A, female versus male mice, and the effect of dexamethasone intervention treatment initiated at different time points after arthritis induction. Hind paws were embedded undecalcified in methyl methacrylate, and sections were stained with Masson-Goldner trichrome. Areal Bone Mineral Density (aBMD) of the femora was determined with pDXA. RNA was extracted from the hind paws followed by the quantification by reverse transcriptase PCR. SKG mice stimulated with mannan presented a higher arthritis score than mice stimulated with zymosan A. Female SKG mice developed a more severe arthritis than male SKG mice. Dexamethasone inhibited arthritis clinically as well as histologically when the treatment was initiated prophylactically or within the first week of arthritis. Femoral aBMD was lower in animals with arthritis than in control animals. The RANKL RNA expression was elevated in arthritic mice, whereas OPG RNA expression was unchanged. The results suggest mannan as arthritis inductor and female instead of male mice in experiments as well as an optimal time window for the initiation of treatment. Systemic bone loss as well as local up regulation of RANKL was present early in SKG arthritis. These results demonstrate that SKG arthritis is a suitable new model for evaluating therapies in RA.
目的是进一步描述 SKG 类风湿关节炎 (RA) 模型及其用于研究干预治疗的潜力，特别关注针对骨骼的治疗方法。进行了三项独立研究，总共使用了 71 只 SKG 小鼠，比较了甘露聚糖与酵母聚糖 A、雌性与雄性小鼠在关节炎诱导方面的差异，以及在关节炎诱导后不同时间点开始地塞米松干预治疗的效果。后爪未经脱钙嵌入甲基丙烯酸甲酯中，并使用 Masson-Goldner 三色染色进行染色。使用 pDXA 测定股骨的面积骨密度 (aBMD)。从后爪提取 RNA，然后通过逆转录 PCR 进行定量。用甘露聚糖刺激的 SKG 小鼠比用酵母聚糖 A 刺激的小鼠表现出更高的关节炎评分。雌性 SKG 小鼠比雄性 SKG 小鼠发展出更严重的关节炎。当预防性或在关节炎发生的第一周内开始治疗时，地塞米松可在临床上和组织学上抑制关节炎。患有关节炎的动物的股骨 aBMD 低于对照动物。关节炎小鼠的 RANKL RNA 表达升高，而 OPG RNA 表达不变。结果表明，甘露聚糖可作为关节炎诱导剂，雌性而非雄性小鼠可用于实验，并且治疗的最佳起始时间窗口。SKG 关节炎中存在系统性骨质流失和局部 RANKL 上调。这些结果表明，SKG 关节炎是评估 RA 治疗方法的一种合适的新型模型。
