Klotho inhibits H 2 O 2 -induced oxidative stress and apoptosis in periodontal ligament stem cells by regulating UCP2 expression

Abstract

Background 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. However, the etiology of periodontitis remains unclear. Klotho, a single-pass transmembrane protein, has been widely reported to modulate cellular processes in various diseases. However, the role of Klotho in periodontitis is unknown.Results In this study, we designed and conducted a series of experiments to evaluate the role of Klotho in chronic periodontitis. 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. Besides, Klotho upregulated the production of uncoupling protein 2 (UCP2) in H2O2-treated PDLSCs. In function, Klotho inhibited H2O2-induced oxidative stress and cellular apoptosis in PDLSCs. Moreover, the rescue assay suggested that UCP2 knock-down suppressed the effects of Klotho on H2O2-induced oxidative stress and apoptosis in PDLSCs.Conclusions In conclusion, we found that Klotho inhibits H2O2-induced oxidative stress and apoptosis in PDLSCs by regulating UCP2 expression. This novel discovery may provide a potential target for chronic periodontitis treatment.

Effects of chronic kidney disease on cognitive function and α-klotho expression in hippocampus

“…Previous studies have shown that α-KL is not only involved in the regulation of calcium and phosphorus metabolism and the inhibition of renal fibrosis in CKD (7,8), but as an in-vivo hormone, it also exerts anti-oxidative stress, anti-inflammatory, anti-apoptotic, and autophagy-regulating effects (9)(10)(11)(12). Under normal renal physiological conditions, α-KL, fibroblast growth factor receptor-1 (FGFR1) and fibroblast growth factor-23 (FGF23) bind to form a trimeric complex, which drives FGF23 phosphorylation and thus reduces serum Pi by inhibiting 1,25-dihydroxyvitamin D and parathyroid hormone synthesis, intestinal Pi absorption, and Pi reabsorption (13,14).…”