Department of Orthodontics, School of Stomatology, Shandong University, Jinan, Shandong Province, People's Republic of China; Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Wenhua Xi Road No. 44-1, Jinan, Shandong Province, People's Republic of China.
Department of Prosthodontics, School of Stomatology, the Fourth Military Medical University, Xi'an, People's Republic of China; Department of Stomatology, PLA 960th Hospital, Jinan, Shandong Province, People's Republic of China.
Gene. 2021 Feb 5;768:145318. doi: 10.1016/j.gene.2020.145318. Epub 2020 Nov 20.
Temporomandibular joint osteoarthritis (TMJ-OA) is one of the most common joint diseases. It causes severe pain and poor quality of life. One key feature of TMJ-OA is degeneration of the chondrocyte extracellular matrix (ECM). Low-intensity pulsed ultrasound (LIPUS) can promote the synthesis of ECM in cartilage. However, the exact mechanism is still unclear. We aimed to explore the mechanism by which LIPUS promotes the expression of aggrecan in chondrocytes. In vivo, TMJ-OA rats established by unilateral occlusal trauma were treated with LIPUS. In our RNA sequencing data, we found that ADAMTS-8 was downregulated by LIPUS. In vitro, chondrocytes were treated with IL-1β and LIPUS. Among Zn exporters, ZNT-9 was specifically upregulated by LIPUS. Activation of ZNT-9 by LIPUS downregulated ECM-degrading enzymes (MMP-3, ADAMTS-5 and ADAMTS-8) and metal regulatory transcription factor-1 (MTF-1) and upregulated aggrecan in chondrocytes. Furthermore, ZNT-9 knockdown caused upregulation of MMP-3, ADAMTS-5, ADAMTS-8 and MTF-1, with concomitant downregulation of aggrecan. The opposite results were obtained after ZNT-9 overexpression. Our experiments demonstrate that LIPUS protects chondrocytes by increasing the expression of aggrecan through ZNT-9.
颞下颌关节骨关节炎（TMJ-OA）是最常见的关节疾病之一。它会导致严重的疼痛和生活质量下降。TMJ-OA 的一个关键特征是软骨细胞细胞外基质（ECM）的退化。低强度脉冲超声（LIPUS）可以促进软骨中 ECM 的合成。然而，其确切机制仍不清楚。我们旨在探讨 LIPUS 促进软骨细胞中聚集蛋白聚糖表达的机制。在体内，通过单侧咬合创伤建立 TMJ-OA 大鼠模型，并用 LIPUS 进行治疗。在我们的 RNA 测序数据中，我们发现 LIPUS 下调了 ADAMTS-8。在体外，用 IL-1β 和 LIPUS 处理软骨细胞。在 Zn 外排体中，LIPUS 特异性地上调了 ZNT-9。LIPUS 激活 ZNT-9 下调了 ECM 降解酶（MMP-3、ADAMTS-5 和 ADAMTS-8）和金属调节转录因子-1（MTF-1），并上调了软骨细胞中的聚集蛋白聚糖。此外，ZNT-9 敲低导致 MMP-3、ADAMTS-5、ADAMTS-8 和 MTF-1 的上调，同时聚集蛋白聚糖的下调。过表达 ZNT-9 则得到相反的结果。我们的实验表明，LIPUS 通过增加 ZNT-9 的表达来保护软骨细胞，从而增加聚集蛋白聚糖的表达。
