Abstract：
Temporomandibular joint osteoarthritis (TMJ OA) is characterized by the degeneration of cartilage and subchondral bone. In this study, we observed a significant increase in cell-free DNA (cfDNA) levels during the progression of TMJ OA. Bioinformatics analysis identified TLR9 as a pivotal molecule in TMJ OA pathogenesis. The polyamidoamine (PAMAM) dendrimer characterized by a well-structured, highly branched, and reactive nature, exhibits robust binding and clearance capabilities for cfDNA. However, the abundant amino groups on the surface of PAMAM lead to its inherent toxicity. To mitigate this, PEG-5000 was conjugated to the surface of PAMAM dendrimers, enhancing safety. Our results indicate that PEG-PAMAM effectively inhibits the upregulation of the TLR9 protein in TMJ OA, significantly suppressing the activation of the p-IκBα/p-NF-κB signaling pathway and subsequently decreasing chondrocyte inflammation and apoptosis, as evidenced by both in vivo and in vitro experiments. We conclude that PEG-PAMAM is a safe and effective material for in vivo applications, offering a promising therapeutic strategy for TMJ OA by targeting cfDNA clearance.
摘要：
颞下颌关节骨关节炎（TMJOA）的特征是软骨和软骨下骨的退化。在这项研究中,我们观察到在TMJOA进展过程中,无细胞DNA(cfDNA)水平显著升高.生物信息学分析确定TLR9是TMJOA发病机制中的关键分子。聚酰胺胺（PAMAM）树枝状聚合物的特征是结构良好，高度分枝,和反应性质，对cfDNA表现出强大的结合和清除能力。然而,PAMAM表面丰富的氨基导致其固有毒性。为了缓解这种情况，PEG-5000与PAMAM树枝状聚合物的表面缀合，提高安全性。我们的结果表明，PEG-PAMAM有效抑制TMJOA中TLR9蛋白的上调，显著抑制p-IκBα/p-NF-κB信号通路的激活，随后减少软骨细胞炎症和凋亡，体内和体外实验都证明了这一点。我们得出结论，PEG-PAMAM是一种安全有效的体内应用材料，通过靶向cfDNA清除为TMJOA提供有希望的治疗策略。
