Department of Orthodontics, School and Hospital of Stomatology, China Medical University, Shenyang, China.
Department of Oral Pathology, School and Hospital of Stomatology, China Medical University, Shenyang, China.
Oral Dis. 2024 May;30(4):2425-2438. doi: 10.1111/odi.14615. Epub 2023 May 15.
To evaluate the role of Piezo1 in the malocclusion-induced osteoarthritic cartilage of the temporomandibular joint.
A temporomandibular joint osteoarthritis model was established using a unilateral anterior crossbite in vivo, and cartilage degeneration and Piezo1 expression were observed by histological and immunohistochemical staining. ATDC5 cells were loaded with 24 dyn/cm fluid flow shear stress using the Flexcell device in vitro and expression and function of Piezo1 were evaluated. After identifying the function of Piezo1 in YAP translocation under FFSS conditions, the influence of Piezo1 and YAP on metabolism-related enzymes under FFSS was detected through a real-time polymerase chain reaction analysis and western blotting. A UAC-TMJ injection model was established to observe the therapeutic effect of intra-articular injection of a Piezo1 inhibitor on osteoarthritic cartilage matrix loss.
Piezo1 was overexpressed in the osteoarthritic cartilage and cultured chondrocytes under shear stress. Piezo1 Silencing inhibited the nuclear translocation of YAP and subsequently downregulated the expression of MMP13 and ADAMTS5. Intra-articular injection of the Piezo1 inhibitor, GsMTx4, could ameliorate proteoglycan degradation in malocclusion-induced TMJOA and suppressed MMP13 and ADAMTS5 expression.
Our results revealed that the activation of Piezo1 promotes mechanical-induced cartilage degradation through the YAP-MMP13/ADAMTS5 signaling pathway.
评估 Piezo1 在颞下颌关节（TMJ）错合诱导性骨关节炎软骨中的作用。
采用单侧前牙反合建立 TMJOA 动物模型，通过组织学和免疫组织化学染色观察软骨退变和 Piezo1 表达。体外使用 Flexcell 装置对 ATDC5 细胞加载 24 dyn/cm 流体力剪切应力，评估 Piezo1 的表达和功能。鉴定 Piezo1 在 FFSS 条件下对 YAP 易位的作用后，通过实时聚合酶链反应分析和 Western blot 检测 Piezo1 和 YAP 对 FFSS 下代谢相关酶的影响。建立 UAC-TMJ 注射模型，观察关节内注射 Piezo1 抑制剂对骨关节炎软骨基质丢失的治疗效果。
剪切应力下，Piezo1 在骨关节炎软骨和培养软骨细胞中过度表达。Piezo1 沉默抑制了 YAP 的核易位，随后下调了 MMP13 和 ADAMTS5 的表达。关节内注射 Piezo1 抑制剂 GsMTx4 可改善错合诱导的 TMJOA 中蛋白聚糖降解，并抑制 MMP13 和 ADAMTS5 的表达。
我们的研究结果表明，Piezo1 的激活通过 YAP-MMP13/ADAMTS5 信号通路促进机械诱导的软骨降解。
