Low-intensity pulsed ultrasound promotes aggrecan expression via ZNT-9 in temporomandibular joint chondrocytes
Low-intensity pulsed ultrasound promotes aggrecan expression via ZNT-9 in temporomandibular joint chondrocytes
复制标题
低强度脉冲超声通过 ZNT-9 促进颞下颌关节软骨细胞中聚集蛋白聚糖的表达
DOI：
10.1016/j.gene.2020.145318
复制
发表时间：
2021-01-05
期刊：
影响因子：
3.5
通讯作者：
Chen, Lei
中科院分区：
文献类型：
--
作者：
He, Dong;Wang, Jing;Chen, Lei
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差。TMJ-OA的一个关键特征是软骨细胞外基质（ECM）的变性。低强度脉冲超声（LIPUS）可促进软骨细胞外基质的合成。然而，确切的机制仍不清楚。我们的目的是探讨LIPUS促进软骨细胞中聚集蛋白聚糖表达的机制。在体内，对单侧咬合创伤建立的TMJ-OA大鼠进行LIPUS治疗。在我们的RNA测序数据中，我们发现ADAMTS-8被LIPUS下调。在体外，软骨细胞用IL-1 β和LIPUS处理。在Zn 2+输出者中，ZNT-9被LIPUS特异性上调。通过LIPUS激活ZNT-9下调ECM降解酶（MMP-3、ADAMTS-5和ADAMTS-8）和金属调节转录因子-1（MTF-1），并上调软骨细胞中的聚集蛋白聚糖。此外，ZNT-9敲低引起MMP-3、ADAMTS-5、ADAMTS-8和MTF-1的上调，伴随着聚集蛋白聚糖的下调。ZNT-9过表达后获得相反的结果。我们的实验表明，LIPUS通过ZNT-9增加聚集蛋白聚糖的表达来保护软骨细胞。
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-1 beta and LIPUS. Among Zn2+ 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.