Osteocytes sense extracellular mechanical stimuli and transduce them into biochemical signals to regulate bone remodeling. The function is also evidenced in orthodontic tooth movement. But the underlying mechanisms haven't been clarified. Autophagy is an evolutionarily conserved cellular catabolic process which affects cellular secretory capabilities. We hypothesized that mechanical force activated osteocyte autophagy through TFE3-related signaling and further promoted osteocyte-mediated osteoclastogenesis. In the present study, we demonstrated that osteocyte autophagy was activated under mechanical compressive force using murine orthodontic tooth movement model since the number of LC3B-positive osteocytes increased by 3-fold in the compression side. In addition, both in vitro mechanical compression and chemical autophagy agonist increased the secretion of RANKL in osteocytes by 3-fold and 4-fold respectively, which is a crucial cytokine for osteoclastogenesis. Lastly, conditioned medium collected from compressed osteocytes promoted the development of osteoclasts. These results suggest that osteocytes could promote osteoclastogenesis via autophagy-mediated RANKL secretion under mechanical compressive force. Our research might provide evidence for exploring methods to accelerate tooth movement in clinic.

骨细胞感觉到细胞外的机械刺激，并将其转化为生化信号以调节骨骼重塑。正畸牙齿运动也证明了这一功能。但是尚未阐明其基本机制。自噬是影响细胞分泌能力的进化保守的细胞分解代谢过程。我们假设机械力通过TFE3相关信号激活骨细胞自噬，并进一步促进骨细胞介导的破骨细胞生成。在本研究中，我们证明了使用鼠正畸牙齿运动模型在机械压缩力下激活了骨细胞自噬，因为在压缩侧LC3B阳性骨细胞的数量增加了3倍。此外，体外机械压缩和化学自噬激动剂均能使破骨细胞中RANKL的分泌分别增加3倍和4倍，这是破骨细胞形成的关键细胞因子。最后，从压缩的骨细胞中收集的条件培养基促进了破骨细胞的发育。这些结果表明，骨细胞可以在机械压力下通过自噬介导的RANKL分泌促进破骨细胞的生成。我们的研究可能为探索加速临床牙齿移动的方法提供证据。这些结果表明，骨细胞可以在机械压力下通过自噬介导的RANKL分泌促进破骨细胞的生成。我们的研究可能为探索加速临床牙齿移动的方法提供证据。这些结果表明，骨细胞可以在机械压力下通过自噬介导的RANKL分泌促进破骨细胞的生成。我们的研究可能为探索加速临床牙齿移动的方法提供证据。