Role of integrin‑linked kinase in static compressive stress‑induced autophagy via phosphatidylinositol 3 kinase in human periodontal ligament cells

Zou,Rui; Wu,Shiyang; Wang,Yijie; Kang,Xueping; Zhao,Shuyang; Shi,Haoyu; Zheng,Danqing; Gao,Bei; Ma,Shuyu; Niu,Lin; Gao,Yunan

doi:10.3892/ijmm.2021.5000

Role of integrin‑linked kinase in static compressive stress‑induced autophagy via phosphatidylinositol 3 kinase in human periodontal ligament cells

Authors:
- Rui Zou
- Shiyang Wu
- Yijie Wang
- Xueping Kang
- Shuyang Zhao
- Haoyu Shi
- Danqing Zheng
- Bei Gao
- Shuyu Ma
- Lin Niu
- Yunan Gao
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Affiliations: Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
Published online on: July 7, 2021 https://doi.org/10.3892/ijmm.2021.5000
Article Number: 167
Copyright: © Zou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Orthodontic tooth movement (OTM) is achieved by using mechanical stimuli, which lead to the remodeling of periodontal tissues. Previous findings have demonstrated that autophagy may be one of the cell responses to mechanical stress. As a key structure in the integrin pathway, integrin linked‑kinase (ILK) may play a role in the transmission of these mechanical signals. In addition, ILK is an important upstream molecule that regulates autophagy, under the influence of phosphatidylinositol 3 kinase (PI3K). Therefore, exploring the effect of mechanical stress on autophagy and the associated role of ILK/PI3K is of utmost significance to understanding the mechanism behind OTM. In the present study, human periodontal ligament cells (hPDLCs) were embedded into a collagen‑alginate complex hydrogel for three‑dimensional (3D) culturing. Static compressive stress (2.5 g/cm²) was loaded using the uniform weight method for 5, 15, 30, and 60 min. The autophagy of hPDLCs was detected by the expression of Beclin‑1 (BECN1) and ATG‑5 using RT‑qPCR and LC3, respectively, using immunofluorescence. The results showed that the level of autophagy and gene expression of ILK increased significantly under static compressive stress. In ILK‑silenced cells, static compressive stress could also upregulate ILK expression and increase the levels of autophagy. After PI3K inhibition, the increase in the autophagy level and the upregulation of ILK expression disappeared. These findings suggest that static compressive stress can induce autophagy in hPDLCs in a rapid, transient process, regulated by ILK and PI3K. Moreover, this static stress can upregulate ILK expression in a PI3K‑dependent manner.

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