Early supplemental 2-macroglobulin attenuates cartilage and bone damage by inhibiting inflammation in collagen II-induced arthritis model
Early supplemental 2-macroglobulin attenuates cartilage and bone damage by inhibiting inflammation in collagen II-induced arthritis model
复制标题
早期补充 2-巨球蛋白通过抑制 II 型胶原诱导的关节炎模型中的炎症来减轻软骨和骨损伤
DOI：
10.1111/1756-185x.13457
复制
发表时间：
2019-04-01
影响因子：
2.5
通讯作者：
Wei, Lei
中科院分区：
文献类型：
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作者：
Li, Shengchun;Xiang, Chuan;Wei, Lei
目的探讨早期关节内补充β 2-巨球蛋白（A2 M）对胶原诱导的关节炎（CIA）小鼠软骨的保护作用。方法DBA/1小鼠随机分为4组（n=15/组）：（a）CIA+1.2 g A2 M;（B）CIA+0.8 g A2 M;（c）CIA+0.4 g A2 M;（d）赋形剂+磷酸盐缓冲液（PBS）。在第36、43和50天，将A2 M注射到右脚踝中，同时将PBS注射到左脚踝中作为内部对照。从第21天开始每隔一天记录CIA炎症临床评分和踝关节厚度，直至处死。通过体内荧光分子断层扫描（FMT）监测炎症的变化。通过X线、组织学和免疫组织化学方法评估炎症、软骨和骨损伤。通过实时聚合酶链反应（PCR）定量测定软骨和炎症相关基因的表达。第43天后，与PBS治疗的踝关节相比，A2 M治疗的踝关节的临床评分、踝关节厚度和Sharp/货车der Heijde方法评分较低。FMT数据表明，炎症标志物MMPSense和ProSense在PBS治疗的踝关节中比A2 M治疗的踝关节显著升高。组织学和X射线分析表明，A2 M管理导致较低水平的炎症浸润和滑膜增生，以及更典型的软骨和骨组织与增加COL II和聚集蛋白聚糖染色相比，PBS处理的脚踝。此外，实时荧光定量PCR显示，基质金属蛋白酶-3，9，-13，COL X和Runx 2的表达显着减少A2 M治疗组比PBS治疗animals.ConclusionEarly补充关节内A2 M发挥抗炎作用，减轻软骨和骨损伤的CIA模型。
ObjectiveTo determine if early supplemental intra-articular 2-macroglobulin (A2M) has a chondroprotective effect in a collagen II-induced arthritis (CIA) mice model.MethodsDBA/1 mice were randomized into four groups (n=15/group): (a) CIA+1.2g of A2M; (b) CIA+0.8g of A2M; (c) CIA+0.4g of A2M; (d) vehicle+phosphate-buffered saline (PBS). A2M was injected into right ankles and PBS was injected into the left ankles simultaneously as internal control at days 36, 43 and 50. The CIA inflammation clinical score and ankle thickness were recorded every other day starting on day 21 until sacrifice. Changes in inflammation were monitored by in vivo fluorescence molecular tomography (FMT). Inflammation, cartilage and bone damage were assessed with X-ray, histology and immunohistochemistry. Cartilage and inflammation-related gene expression was quantified by real-time polymerase chain reaction (PCR).ResultsAll mice showed ankle inflammation on day 33. After day 43, lower clinical scores, ankle thickness and Sharp/van der Heijde method scores in A2M-treated ankles compared with PBS-treated ankles. FMT data indicated that the inflammation markers MMPSense and ProSense were significantly elevated in the PBS-treated ankles than A2M-treated ankles. Histology and X-ray analyses indicated that A2M administration resulted in lower levels of inflammatory infiltration and synovial hyperplasia, as well as more typical cartilage and bone organization with increased COL II and Aggrecan staining when compared with PBS-treated ankles. In addition, real-time PCR showed that,matrix metalloproteinase-3, -9, -13, COL X and Runx2 were significantly less expressed in A2M-treated groups than PBS-treated animals.ConclusionEarly supplemental intra-articular A2M exerts an anti-inflammatory effect and attenuates cartilage and bone damage in a CIA model.