Department of Temporomandibular Joint, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510140, China.
Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou 510182, China.
ACS Appl Mater Interfaces. 2024 Jul 31;16(30):39153-39164. doi: 10.1021/acsami.4c08569. Epub 2024 Jul 17.
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.
颞下颌关节骨关节炎（TMJ OA）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 TMJ OA 的进展过程中细胞游离 DNA（cfDNA）水平显著增加。生物信息学分析确定 TLR9 是 TMJ OA 发病机制中的关键分子。聚酰胺-胺（PAMAM）树枝状大分子具有结构良好、高度分支和反应性的特点，对 cfDNA 具有强大的结合和清除能力。然而，PAMAM 表面丰富的氨基会导致其固有毒性。为了解决这个问题，PEG-5000 被接枝到 PAMAM 树枝状大分子的表面，提高了安全性。我们的结果表明，PEG-PAMAM 能有效抑制 TMJ OA 中 TLR9 蛋白的上调，显著抑制 p-IκBα/p-NF-κB 信号通路的激活，进而减少软骨细胞的炎症和凋亡，这在体内和体外实验中都得到了证实。我们得出结论，PEG-PAMAM 是一种安全有效的体内应用材料，通过清除 cfDNA 为 TMJ OA 提供了一种有前景的治疗策略。
