College of Stomatology, Chongqing Medical University, Chongqing, China.
Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China.
J Cell Mol Med. 2024 Jun;28(11):e18472. doi: 10.1111/jcmm.18472.
Excessive load on the temporomandibular joint (TMJ) is a significant factor in the development of TMJ osteoarthritis, contributing to cartilage degeneration. The specific mechanism through which excessive load induces TMJ osteoarthritis is not fully understood; however, mechanically-activated (MA) ion channels play a crucial role. Among these channels, Piezo1 has been identified as a mediator of chondrocyte catabolic responses and is markedly increased in osteoarthritis. Our observations indicate that, under excessive load conditions, endoplasmic reticulum stress in chondrocytes results in apoptosis of the TMJ chondrocytes. Importantly, using the Piezo1 inhibitor GsMTx4 demonstrates its potential to alleviate this condition. Furthermore, Piezo1 mediates endoplasmic reticulum stress in chondrocytes by inducing calcium ion influx. Our research substantiates the role of Piezo1 as a pivotal ion channel in mediating chondrocyte overload. It elucidates the link between excessive load, cell apoptosis, and calcium ion influx through Piezo1. The findings underscore Piezo1 as a key player in the pathogenesis of TMJ osteoarthritis, shedding light on potential therapeutic interventions for this condition.
颞下颌关节（TMJ）的过度负荷是 TMJ 骨关节炎发展的一个重要因素，导致软骨退化。过度负荷诱导 TMJ 骨关节炎的确切机制尚不完全清楚；然而，机械激活（MA）离子通道起着关键作用。在这些通道中，Piezo1 已被确定为软骨细胞分解代谢反应的介质，并且在骨关节炎中显著增加。我们的观察表明，在过度负荷条件下，软骨细胞内质网应激导致 TMJ 软骨细胞凋亡。重要的是，使用 Piezo1 抑制剂 GsMTx4 表明其具有缓解这种情况的潜力。此外，Piezo1 通过诱导钙离子内流介导软骨细胞内质网应激。我们的研究证实了 Piezo1 作为介导软骨细胞过载的关键离子通道的作用。它阐明了通过 Piezo1 连接过度负荷、细胞凋亡和钙离子内流之间的关系。这些发现强调了 Piezo1 在 TMJ 骨关节炎发病机制中的关键作用，为这种疾病的潜在治疗干预提供了线索。
