McCaig Institute for Bone and Joint Health, Faculty of Medicine, University of Calgary, 3330 Hospital Drive N.W., Calgary, Alberta, T2N 4N1, Canada; Department of Medical Science, Faculty of Medicine, University of Calgary, 3330 Hospital Drive N.W., Calgary, Alberta, T2N 4N1, Canada.
J Orthop Res. 2014 Apr;32(4):566-72. doi: 10.1002/jor.22568. Epub 2013 Dec 30.
Corticosteroids are used in musculoskeletal diseases, and offer patient relief. Injections of corticosteroids are recommended for management of osteoarthritis (OA). Current data have shown the role of corticosteroids in ameliorating pain. We hypothesized that repeated intra-articular injections of high dose dexamethasone would protect the cartilage from damage in a post-traumatic model of OA. Eighteen female New Zealand White rabbits were used. Twelve underwent surgery to induce OA; six of them received intra-articular injections of dexamethasone every 3 days for 3 weeks. The other six rabbits served as operated controls. Six additional rabbits served as non-operated controls. All animals were euthanized 3 weeks post-surgery. Knees were assessed grossly. Cartilage, synovium, and fat pad were assessed histologically. Synovium and fat pad were analyzed with qPCR and Western blots. Surgical controls had cartilage damage which was supressed with dexamethasone. Dexamethasone significantly decreased synovial expression of interleukin-1β and collagen I, and a trend to decrease synovial matrix metalloproteinase3 expression. There were also significantly lower levels of interleukin-1β protein with dexamethasone treatment. Dexamethasone significantly decreased fat pad expression of matrix metalloproteinase13, basic fibroblast growth factor, and interleukin8, and a trend to decrease matrix metalloproteinase3 and transforming growth factorβ expression. Dexamethasone decreased joint inflammation and joint tissue degradation and was chondroprotective in this unique model of PTOA.
皮质类固醇被用于治疗肌肉骨骼疾病，并为患者带来缓解。皮质类固醇注射被推荐用于治疗骨关节炎（OA）。目前的数据表明皮质类固醇在缓解疼痛方面具有作用。我们假设，在创伤后 OA 模型中，重复关节内注射高剂量地塞米松将保护软骨免受损伤。
使用了 18 只雌性新西兰白兔。12 只兔子接受手术以诱导 OA；其中 6 只兔子每 3 天接受一次关节内注射地塞米松，共 3 周。另外 6 只兔子作为手术对照。另外 6 只兔子作为非手术对照。所有动物在手术后 3 周被安乐死。对膝关节进行大体评估。对软骨、滑膜和脂肪垫进行组织学评估。用 qPCR 和 Western blot 分析滑膜和脂肪垫。手术对照动物的软骨损伤被地塞米松抑制。地塞米松显著降低了滑膜中白细胞介素-1β和胶原 I 的表达，并呈降低滑膜基质金属蛋白酶 3 表达的趋势。地塞米松治疗后白细胞介素-1β蛋白水平也显著降低。地塞米松显著降低了脂肪垫中基质金属蛋白酶 13、碱性成纤维细胞生长因子和白细胞介素 8 的表达，并呈降低基质金属蛋白酶 3 和转化生长因子β表达的趋势。地塞米松减少了关节炎症和关节组织降解，在这种独特的 PTOA 模型中具有软骨保护作用。
