Abstract
Human periodontal ligament stem cells (hPDLSCs) are a favourable source for tissue engineering, but oxidative stress conditions during cell culture and transplantation could affect stem cell viability and stemness, leading to failed regeneration. The aim of this study was to evaluate the antioxidant and protective effects of Klotho, an antiageing protein, against cell damage and the loss of osteogenesis in hPDLSCs in H2O2-induced oxidative environments. H2O2 was used as an exogenous reactive oxygen species (ROS) to induce oxidative stress. Recombinant human Klotho protein was administered before H2O2 treatment. Multitechniques were used to assess antioxidant activity, cell damage, and osteogenic ability of hPDLSCs in oxidative stress and the effects of Klotho on hPDLSCs. Mitochondrial function was analyzed by an electron microscopy scan of cellular structure, mitochondrial DNA copy number, and cellular oxygen consumption rate (OCR). Furthermore, we explored the pathway by which Klotho may function to regulate the antioxidant system. We found that pretreatment with recombinant human Klotho protein could enhance SOD activity and reduce intracellular oxidative stress levels. Klotho reduced H2O2-induced cellular damage and eventually maintained the osteogenic differentiation potential of hPDLSCs. Notably, Klotho promoted mitochondrial function and activated antioxidants by negatively regulating the PI3K/AKT/FoxO1 pathway. The findings suggest that Klotho protein enhanced the antioxidative ability of hPDLSCs and protected stem cell viability and stemness from H2O2-induced oxidative stress by restoring mitochondrial functions and the antioxidant system.
Highlights
Periodontitis is a chronic inflammatory disease that causes the destruction of tooth-supporting tissues and the progressive loss of periodontal attachment and alveolar bone [1, 2]
The cells possessed the ability to differentiate into osteoblasts and adipocytes. These results suggested that the cells we isolated from human periodontal ligament tissue were Mesenchymal stem cells (MSCs) (Figure S1)
The results showed that Klotho ameliorated H2O2-induced cytotoxicity in Human periodontal ligament stem cells (hPDLSCs), and the effect peaked at a concentration of 100 ng/mL (Figure 1(c))
Summary
Periodontitis is a chronic inflammatory disease that causes the destruction of tooth-supporting tissues and the progressive loss of periodontal attachment and alveolar bone [1, 2]. Periodontitis is the major cause of tooth loss in adults, treatments of periodontitis are far from satisfactory. Mesenchymal stem cells (MSCs) are emerging as major sources for cell-based tissue engineering due to their immunity privilege [6]. Being more accessible and possessing higher cell growth than human bone marrow stem cells (hBMMSCs) do, hPDLSCs have important homeostatic functions in vivo and display angiogenic, immunomodulatory, and multilineage differentiative capacity in vitro [7,8,9]. With the osteoblastic differentiation ability, hPDLSCs are capable for repairing alveolar bone defect and periodontal intrabony defects [13, 14]
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