Cellular senescence of RANKL⁺ osteoblasts and Th17 cells in severe periodontitis with occlusal trauma

Abstract

Purpose: Excessive occlusal forces resulting from inadequate dental prosthesis, along with periodontal infection (PI), lead to severe periodontitis; however, the roles of senescent cells and their involvement in the mechanisms underlying this process remain unclear. Therefore, this study aimed to elucidate the roles of senescent cells and their cell types in severe periodontitis with excessive force (occlusal trauma [OT]).

Methods: To determine whether senescent cells exacerbate alveolar bone resorption, we developed a severe periodontitis rat model by inducing PI and OT and assessed the presence of senescent cells and bone resorption. Senolytics (dasatinib + quercetin [DQ]) were administered to evaluate the changes in the appearance of senescent cells and bone resorption.

Results: PI and OT + PI increased senescent cells as well as osteoclasts. Furthermore, p21 and receptor activator of nuclear factor-kappa B ligand (RANKL) co-expressing cells were observed in the OT + PI group rats, suggesting a correlation between bone resorption and senescent cells. Cell type analysis identified osteoblasts and Th17 cells as RANKL⁺ cells expressing p21 or p16. DQ administration reduced senescent cells and osteoclasts, thereby preventing alveolar bone resorption.

Conclusions: RANKL⁺ senescent osteoblasts and Th17 cells are involved in osteoclastogenesis and bone resorption. Our findings highlight a new target for the prosthetic treatment of severe periodontitis.