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

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/cm 2 ) 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.

Programmed cell death of periodontal ligament cells

“…Targeted drug therapies that regulate cell death in clinical practice represent a strategy against tooth root resorption. However, the specific Interestingly, autophagy may be a single cellular response to mechanical stress (Zou et al, 2021) and may play a protective role in the early stages to prevent cell death. However, the effect gradually weakens and disappears with the duration of application.…”

“…It is generally believed that exposure to appropriate stress stimuli can promote osteoclast differentiation and osteoblast apoptosis, which is the fundamental principle of OTM. Interestingly, autophagy may be a single cellular response to mechanical stress (Zou et al, 2021) and may play a protective role in the early stages to prevent cell death. However, the effect gradually weakens and disappears with the duration of application.…”