2023, Vol. 27 ›› Issue (5): 683-689

Correlation between autophagy and the Hippo-YAP protein pathway in periodental ligament cells on the pressure side of a mouse model of orthodontic tooth movement

Wu Yujie1, 2, Wan Xiaofang1, 2, Wei Mianxing1, 2, Peng Shiyuan1, 2, Xu Xiaomei1, 2   

Abstract: BACKGROUND: Autophagy is involved in the response of periodontal ligament cells to orthodontic forces, but how mechanical stimulation induces autophagy remains unclear. The Hippo-Yes-associated protein (YAP) pathway is sensitive to mechanical stimulation and is involved in the regulation of autophagy.
OBJECTIVE: To observe changes of the Hippo-YAP pathway and autophagy-related factors in the pressure side of orthodontic teeth and to explore whether the Hippo-YAP pathway is involved in the response of periodontal ligament cells to mechanical stimulation and its relationship with autophagy.
METHODS: Fifty-four C57BL/6 mice were randomly divided into a blank group and eight experimental groups (orthodontic force applied for 30 minutes, 1 hour, 2 hours, 4 hours, 12 hours, 1 day, 3 days, 7 days). Mice in the experimental groups were modeled and killed at the set time after modeling to take their upper right first molars. Hematoxylin-eosin staining was used to observe the periodontal ligament tissue morphology on the pressure side. Tartrate-resistant acid phosphatase staining was used to count osteoclasts. Expressions of Beclin-1, LC3B, and active-YAP were detected by immunohistochemical staining.
RESULTS AND CONCLUSION: Hematoxylin-eosin staining showed that with the application of orthodontic force, the periodontal ligament on the pressure side was first compressed and then slightly restored. Osteoclasts began to increase in number after 12 hours of orthodontic force applied (P < 0.01), and then the number of cells gradually increased and peaked at 7 days (P < 0.01). In the experimental groups, the expression of Beclin-1 and LC3B in periodontal ligament cells on the pressure side was correlated with the active-YAP expression during tooth movement and they showed similar trends. Correlation analysis showed that Beclin-1 and LC3B were both highly correlated with active-YAP (P < 0.01). These findings indicate that the Hippo-YAP pathway is involved in the response of periodontal ligament cells to mechanical stimulation on the pressure side, which may be an upstream regulation of autophagy. However, further experimental investigations are required.
Key words: orthodontic tooth movement, periodontal ligament, Hippo signaling pathway, Yes-associated protein, autophagy