1. Academic Validation
  2. Osteocytes promote osteoclastogenesis via autophagy-mediated RANKL secretion under mechanical compressive force

Osteocytes promote osteoclastogenesis via autophagy-mediated RANKL secretion under mechanical compressive force

  • Arch Biochem Biophys. 2020 Nov 15;694:108594. doi: 10.1016/j.abb.2020.108594.
Wenlei Li 1 Jing Zhao 1 Wen Sun 1 Hua Wang 2 Yongchu Pan 2 Lin Wang 3 Wei-Bing Zhang 4
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.
  • 2 Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China; Department of Orthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
  • 3 Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China; Department of Orthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China. Electronic address: lw603@njmu.edu.cn.
  • 4 Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China; Department of Orthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China. Electronic address: zhangweibing@njmu.edu.cn.
Abstract

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.

Keywords

Autophagy; Mechanical compression; Osteoclastogenesis; Osteocytes.

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