Mechanical loading and autophagy: A study on the BoNT-A injection-induced condylar cartilage degeneration
Mechanical loading and autophagy: A study on the BoNT-A injection-induced condylar cartilage degeneration
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DOI：
10.1016/j.abb.2023.109788
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发表时间：
2023-10-21
影响因子：
3.9
通讯作者：
Li，Lingjie
中科院分区：
文献类型：
--
作者：
Hou，Siyu;Peng，Sisi;Li，Lingjie
A 型肉毒杆菌毒素 (BoNT-A) 已成为颞下颌关节紊乱病 (TMD) 的一种治疗选择。通过将 BoNT-A 注射到咬肌中，可以减少颞下颌关节 (TMJ) 上的机械负荷。然而，大量先前的研究表明机械负荷的过度减少会对颞下颌关节软骨产生不利影响。这项研究提出，自噬是一种受机械负荷影响的过程，可能在 BoNT-A 诱导的下颌髁软骨退变中发挥作用。为了探索这一假设，我们采用 BoNT-A 注射和过度咬合模型来诱导 C57BL/6 小鼠髁突软骨上机械负荷的变化，从而分别模拟机械负荷的增加和减少。结果显示，注射 BoNT-A 后，软骨厚度显着减少，软骨细胞中 Runt 相关转录因子 2 (Runx2) 表达下调。体外实验表明，软骨细胞中 Runx2 表达的减少与自噬相关，可能依赖于低机械负荷诱导的 YAP 表达减少。这项研究揭示了 YAP/LC3/Runx2 信号通路在 BoNT-A 介导的下颌髁软骨退变中的潜在参与。
Botulinum toxin A (BoNT-A) has emerged as a treatment option for temporomandibular disorder (TMD). By injecting BoNT-A into the masseter muscle, it is possible to reduce mechanical loading on the temporomandibular joint (TMJ). However, numerous prior studies have indicated excessive reduction in mechanical loading can have detrimental effects on TMJ cartilage. This study proposes that autophagy, a process influenced by mechanical loading, could play a role in BoNT-A-induced mandibular condyle cartilage degeneration. To explore this hypothesis, we employed both BoNT-A injection and an excessive biting model to induce variations in mechanical loading on the condyle cartilage of C57BL/6 mice, thereby simulating an increase and decrease in mechanical loading, respectively. Results showed a significant reduction in cartilage thickness and downregulation of Runt-related transcription factor 2 (Runx2) expression in chondrocytes following BoNT-A injection. In vitro experiments demonstrated that the reduction of Runx2 expression in chondrocytes is associated with autophagy, possibly dependent on decreased YAP expression induced by low mechanical loading. This study reveals the potential involvement of the YAP/LC3/Runx2 signaling pathway in BoNT-A mediated mandibular condylar cartilage degeneration.