PTEN Inhibits Inflammatory Bone Loss in Ligature-Induced Periodontitis via IL1 and TNF-α.

Chuanyun Fu,Zhimin Wei,Dongsheng Zhang

doi:10.1155/2019/6712591

Abstract

Phosphatase and tensin homolog (PTEN) is a critical regulator of tumorigenesis and bone remodeling, which is also found expressed in the periodontal tissues. Periodontitis is one of the most common oral diseases and associated with alveolar bone resorption and tooth loosening in adults. However, the functional relevance of PTEN in periodontitis remains unclear. Here, we report that PTEN plays an essential role in periodontitis. The in vivo results of our study showed a significant decrease of PTEN in the ligature-induced mouse periodontitis model. The function of PTEN in the macrophages was shown to be associated with inflammatory factors interleukin 1 (IL1) and tumor necrosis factor (TNF-α) by using overexpression and silence methods. Further mechanistic studies indicated lack of PTEN-activated IL1 and TNF-α, which increased the number of osteoclasts and led to alveolar bone erosion and loss. Moreover, PTEN nanoparticles could directly inhibit the inflammatory process and bone erosion, suggesting a controlling role of PTEN during bone remodeling. All these data identified the novel function of PTEN as a key factor in periodontitis and bone remodeling.

Highlights

Inflammatory osteolysis is a critical pathological feature of clinical inflammatory diseases such as periodontitis which is one of the most common oral diseases and associated with alveolar bone resorption and tooth loosening in adults [1]. e therapeutics for periodontitis are intended to block inflammation locally, but not enough for inflammatory bone destruction [2]
In the pathogenesis of periodontitis, osteolysis is predominantly caused by increased osteoclasts number and activity [3, 4]. e most determined cytokine involved in osteoclastogenesis is the receptor activator of nuclear factor κB ligand (RANKL) [5]
Several studies indicate that the phosphoinositide 3-kinase (PI3K)/PTEN pathway regulates the inflammatory response [8, 9]. e nuclear factor kappa-lightchain-enhancer of activated B cells (NF-κB) pathway is the classical proinflammatory signaling pathway based on the role of NF-κB in proinflammatory gene expressions. e study has shown that Toll-like receptor (TLR)-induced PI3K / Akt activation is phosphorylated, thereby inhibiting downstream glycogen synthase kinase (GSK) 3β, leading to a diminished expression of NF-κB-driven proinflammatory genes in monocytes [10]

Summary

Introduction

Inflammatory osteolysis is a critical pathological feature of clinical inflammatory diseases such as periodontitis which is one of the most common oral diseases and associated with alveolar bone resorption and tooth loosening in adults [1]. e therapeutics for periodontitis are intended to block inflammation locally, but not enough for inflammatory bone destruction [2]. E therapeutics for periodontitis are intended to block inflammation locally, but not enough for inflammatory bone destruction [2]. E most determined cytokine involved in osteoclastogenesis is the receptor activator of nuclear factor κB ligand (RANKL) [5]. Us, an ideal therapeutic strategy to prevent inflammatory bone destruction is to suppress proinflammatory cytokines activation during osteoclastogenesis. E nuclear factor kappa-lightchain-enhancer of activated B cells (NF-κB) pathway is the classical proinflammatory signaling pathway based on the role of NF-κB in proinflammatory gene expressions. E study has shown that Toll-like receptor (TLR)-induced PI3K / Akt activation is phosphorylated, thereby inhibiting downstream glycogen synthase kinase (GSK) 3β, leading to a diminished expression of NF-κB-driven proinflammatory genes in monocytes [10].

Methods

Results

Conclusion