肉毒杆菌毒素A(BoNT-A)已成为颞下颌关节紊乱病(TMD)的治疗选择。通过向咬肌注射BoNT-A,可以减少颞下颌关节(TMJ)的机械负荷。然而,许多先前的研究已经表明机械负荷的过度降低可以对TMJ软骨具有不利影响。本研究提出自噬,受机械载荷影响的过程,可能在BoNT-A诱导的下颌髁突软骨退变中发挥作用。为了探索这个假设,我们采用BoNT-A注射和过度咬伤模型来诱导C57BL/6小鼠髁突软骨的机械负荷变化,从而模拟机械载荷的增加和减少,分别。结果显示BoNT-A注射后软骨细胞中软骨厚度的显著降低和Runt相关转录因子2(Runx2)表达的下调。体外实验表明,软骨细胞中Runx2表达的降低与自噬有关,可能依赖于低机械负荷诱导的YAP表达降低。这项研究揭示了YAP/LC3/Runx2信号通路在BoNT-A介导的下颌髁突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.