Klotho inhibits H2 O2 -induced oxidative stress and apoptosis in periodontal ligament stem cells by regulating UCP2 expression.

Lilei Zhu,Qingqing Liu,Fei Ma,Hui Xie,Hao Wu

doi:10.1111/1440-1681.13547

Abstract

Periodontitis, a human chronic inflammatory disease, has affected the lives of millions of individuals. Periodontal ligament stem cells (PDLSCs), derived from the periodontal ligament, exhibit tissue specificity and impaired differentiation ability and are closely associated with tissue regeneration in periodontitis. Klotho, a single-pass transmembrane protein, has been reported to positively affect H2 O2 -induced oxidative stress and inflammation in PDLSCs. The ultimate damage of oxidative stress stimulation in PDLSCs was cell apoptosis, which was also the major lesion in periodontitis. Thus, the present study aimed to figure out the effect of klotho on H2 O2 -injured PDLSCs and its underlying mechanism to provide new therapeutic targets in periodontitis. The expression of klotho and uncoupling protein 2 (UCP2) was investigated in the gingival tissues, gingival crevicular fluid (GCF), and periodontal ligament stem cells (PDLSCs) in patients with chronic periodontitis. Then, under klotho treatment, oxidative stress was evaluated by measuring SOD and GSH-PX levels. Cell apoptosis and cell necrosis were also detected by measuring the cell death-relevant proteins, including Caspase-3, BAX, Bcl, MLKL, RIP1, and RIP3. Finally, a rescue assay was performed by inhibiting the expression of UCP2. The results showed that klotho and UCP2 were downregulated in patients with chronic periodontitis. In addition, klotho upregulated the production of UCP2 in H2 O2 -treated PDLSCs. Klotho inhibited H2 O2 -induced oxidative stress and cellular loss in PDLSCs, moreover, the rescue assay suggested that UCP2 knockdown suppressed the effects of klotho on PDLSCs. In conclusion, this study showed that klotho inhibits H2 O2 -induced oxidative stress and apoptosis in PDLSCs by regulating UCP2 expression. This novel discovery might provide a potential target for chronic periodontitis treatment.

Highlights

Periodontitis, known as a human chronic inflammatory disease, has affected the life of millions of individuals
Our experimental results showed that Klotho was downregulated in the gingival tissues, gingival crevicular fluid (GCF), and periodontal ligament stem cells (PDLSCs) of chronic periodontitis patients
In conclusion, we found that Klotho inhibits H2O2-induced oxidative stress and apoptosis in PDLSCs by regulating uncoupling protein 2 (UCP2) expression

Summary

Introduction

Periodontitis, known as a human chronic inflammatory disease, has affected the life of millions of individuals Known risk factors such as metabolic disease and oxidative stress have been reported to be closely associated with the initiation or development of periodontitis. Periodontitis is a chronic inflammatory disease characterized with the destruction of the supportive tissues of teeth and periodontal attachment, resulting in tooth loss, and has affected approximately 740 million individuals worldwide [1, 2]. Factors such as destructive immune responses and oxidative stress have been reported to be closely associated with the initiation or development of periodontitis [3, 4]. Evaluation of antioxidant enzymes including superoxide dismutase (SOD) is required to clarify the complex process of oxidative stress [8]

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