Section of Molecular Medicine, Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612, USA.
Osteoarthritis Cartilage. 2011 Apr;19(4):458-65. doi: 10.1016/j.joca.2011.01.012. Epub 2011 Jan 22.
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.
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.
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)-1β, were elevated in arthritic animals. Expression of the IL-1β 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.
We propose that constantly elevated levels of catabolic cytokines, such as IL-1β, 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.
研究颞下颌关节（TMJ）在类风湿关节炎（RA）的自身免疫性小鼠模型中的受累情况，这种疾病的特征是滑膜关节的炎症性破坏。尽管 TMJ 功能障碍在 RA 中经常被发现，但 RA 中 TMJ 的受累情况仍不清楚，并且在 RA 的系统性自身免疫动物模型中尚未研究 TMJ 病理学。
在遗传易感的 BALB/c 小鼠中产生蛋白聚糖（PG）聚集素诱导的关节炎（PGIA）。采集 TMJ 和关节组织/软骨进行组织学和免疫组织化学分析以及定量聚合酶链反应的 RNA 分离。测量急性或慢性关节炎小鼠以及非关节炎对照动物的血清细胞因子水平。
尽管四肢发生了破坏性滑膜炎，但 PGIA 小鼠的 TMJ 中几乎没有或没有滑膜炎。然而，关节炎小鼠的 TMJ 显示出聚集蛋白聚糖酶和基质金属蛋白酶介导的糖胺聚糖含量降低的证据，在最严重的情况下，软骨结构受损。促炎细胞因子（包括白细胞介素（IL）-1β）的血清水平在关节炎动物中升高。炎性肢体中 IL-1β 基因的表达也很高，但 TMJ 中基本正常。降解酶（聚集蛋白聚糖酶和基质溶解素）编码基因在四肢和 TMJ 中的表达均上调到相似程度。
我们提出，循环中不断升高的代谢细胞因子（如 IL-1β）水平（从发炎关节释放）在 TMJ 中产生促炎环境，导致局部上调蛋白水解酶并随后从软骨中丢失聚集蛋白聚糖。
