Fluid shear stress promotes periodontal ligament cells proliferation via p38-AMOT-YAP

• DOI: 10.1007/s00018-022-04591-w
• Publication Date: 2022-10-16T09:02:18Z
• Authors: Qiusheng Shi; Lisha Zheng; Jing Na; Xinyang Li; Zhijie Yang; Xinyuan Chen; Yaxin Song; Chiyu Li; Lulin Zhou; Yubo Fan
• Keywords: 0301 basic medicine; 03 medical and health sciences; Actin Depolymerizing Factors; Angiomotins; Periodontal Ligament; YAP-Signaling Proteins; Proto-Oncogene Proteins c-akt; Actins; Cell Proliferation

Abstract Periodontal ligament (PDL) cells are a promising tool for periodontal regeneration therapy. Achieving a sufficient number of PDL cells is essential to PDL regeneration. In our study, appropriate flow shear stress (FSS, 1–6 dyn/cm2) promotes the proliferation of PDL cells. FSS remodels cytoskeleton and focal adhesion in a duration-dependent manner. FSS induces PDL cells to form the actin cap within 10 min, flattens the nuclei, and increases the nuclear pore size, which promotes nuclear translocation of YAP/TAZ. FSS activates p38, which plays a dual function in YAP/TAZ regulation. p38 regulates the phosphorylation of Akt and cofilin, as well as induced F-actin polymerization to induce YAP/TAZ activity. In addition, p38 inhibits pLATS and consecutively regulates angiomotin (AMOT) and YAP/TAZ phosphorylation. AMOT competitively binds to F-actin and YAP/TAZ to participate in FSS-mediated YAP/TAZ nuclear translocation and cell proliferation. Taken collectively, our results provide mechanistic insights into the role of p38-Amot-YAP/TAZ in FSS-mediated PDL cells proliferation and indicate potential applications in dental regenerative medicine.