Osteoarthritis-like damage of cartilage in the temporomandibular joints in mice with autoimmune inflammatory arthritis
Osteoarthritis-like damage of cartilage in the temporomandibular joints in mice with autoimmune inflammatory arthritis
复制标题
DOI：
10.1016/j.joca.2011.01.012
复制
发表时间：
2011-04-01
影响因子：
7
通讯作者：
Mikecz, K.
中科院分区：
文献类型：
--
作者：
Ghassemi-Nejad, S.;Kobezda, T.;Mikecz, K.
目的：研究以滑膜关节炎症破坏为特征的自身免疫性类风湿关节炎（RA）小鼠模型中颞下颌关节（TMJ）的参与情况。虽然颞下颌关节功能障碍常见于类风湿性关节炎。目前尚不清楚TMJ与RA的关系，也未在RA的全身自身免疫动物模型中研究TMJ病理。方法：在遗传易感的BALB/c小鼠中产生蛋白多糖（PG）聚集蛋白诱导的关节炎（PGIA）。采集TMJs和关节组织/软骨进行组织学和免疫组织化学分析，并分离RNA进行定量聚合酶链反应。测定了急性或慢性关节炎小鼠和非关节炎对照动物的血清细胞因子水平。结果：PGIA小鼠的颞下颌关节中，尽管发生了四肢的破坏性滑膜炎，但滑膜炎症很少或没有发生。然而，关节炎小鼠的TMJs显示了聚集酶和基质金属蛋白酶介导的含糖胺聚糖的聚集蛋白丢失的证据，在最严重的情况下，软骨结构损伤。关节炎动物血清中促炎细胞因子（包括白细胞介素-1 β）水平升高。IL-1 β基因在炎症肢体中的表达也很高，但在颞下颌关节中基本正常。在四肢和颞下颌关节中，编码基质降解酶（聚集酶和基质溶酶）的基因的局部表达也有类似程度的上调。结论：我们认为，循环中不断升高的分解代谢细胞因子，如IL-1 β，（从发炎的关节释放）在TMJ内创造了一个促炎环境，导致局部蛋白水解酶上调，随后软骨聚集蛋白丢失。(C) 2011国际骨关节炎研究学会。Elsevier Ltd.出版。版权所有。
Objective: To study temporomandibular joint (TMJ) involvement in an autoimmune murine model of rheumatoid arthritis (RA), a disease characterized by inflammatory destruction of the synovial joints. Although TMJ dysfunction is frequently found in RA. TMJ involvement in RA remains unclear, and TMJ pathology has not been studied in systemic autoimmune animal models of RA.Methods: Proteoglycan (PG) aggrecan-induced arthritis (PGIA) was generated in genetically susceptible BALB/c mice. TMJs and joint tissues/cartilage were harvested for histological and immunohistochemical analyses and RNA isolation for quantitative polymerase chain-reaction. Serum cytokine levels were measured in mice with acute or chronic arthritis, and in non-arthritic control animals.Results: Despite the development of destructive synovitis in the limbs, little or no synovial inflammation was found in the TMJs of mice with PGIA. However, the TMJs of arthritic mice showed evidence of aggrecanase- and matrix metalloproteinase-mediated loss of glycosaminoglycan-containing aggrecan, and in the most severe cases, structural damage of cartilage. Serum levels of pro-inflammatory cytokines, including interleukin (IL)-1 beta, were elevated in arthritic animals. Expression of the IL-1 beta gene was also high in the inflamed limbs, but essentially normal in the TMJs. Local expression of genes encoding matrix-degrading enzymes (aggrecanases and stromelysin) was upregulated to a similar degree in both the limbs and the TMJs.Conclusion: We propose that constantly elevated levels of catabolic cytokines, such as IL-1 beta, in the circulation (released from inflamed joints) create a pro-inflammatory milieu within the TMJ, causing local upregulation of proteolytic enzymes and subsequent loss of aggrecan from cartilage. (C) 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.