Gold nanoparticles enhance proliferation and osteogenic differentiation of periodontal ligament stem cells by PINK1-mediated mitophagy

Alveolar bone defects are caused by several factors, including periodontitis, trauma, infection, and congenital alveolar fenestration (Elisabet et al., 2013). The clinical effects of both non-surgical and surgical conventional therapies remain limited (Anderson et al., 2022). The use of autologous periodontal ligament stem cells (PDLSCs) in the treatment of periodontal intraosseous defects is safe and does not generate remarkable adverse effects (Chen et al., 2016). Gold nanoparticles (AuNPs) possess multiple outstanding advantages, including unique physicochemical properties, first-class biocompatibility, facile synthetic methods, and surface functionalization (Fan et al., 2020). A striking feature of AuNPs is the ease of controlling their size, shape and surface chemistry during synthesis (Khoobchandani et al., 2020, Kumthekar et al., 2021). At present, several nano-platforms based on AuNPs have been constructed for molecular imaging, drug or gene delivery, stem cell tracking, and tissue engineering. Accumulated evidence proved that AuNPs of a specific size exert a boosting effect on proliferation and osteogenic differentiation of PDLSCs (Li et al., 2018), but the mechanism of this effect is vague.

Mitophagy is a selective autophagic mechanism to remove mitochondria that controls their mass and quantity, clearing away those that are dysfunctional or in excess and producing reactive oxygen species (ROS), leading to cell death (Cen et al., 2022, Michaelis et al., 2022). PTEN-induced putative kinase 1 (PINK1)/Parkin exerts a crucial role in mitochondrial quality control since it performs ubiquitin-dependent mitophagy (Xu et al., 2020). PINK1 is stabilized on the outer mitochondrial membrane when the mitochondrial potential remarkably descends, followed by the recruitment of Parkin from the cytosol to damaged mitochondria to trigger an autophagic flux (Wang et al., 2018). This mechanism contributes to the activation of parkin E3 ligase and ubiquitination of mitochondrial outer membrane proteins, eventually resulting in the removal of damaged mitochondria through mitophagy (Kong et al., 2021). Mitophagy exerts an essential role in the maintenance and differentiation of stem cells, including PDLSCs, potentially protecting stem cells from metabolic stress damage (Lin et al., 2021). PINK1-dependent mitophagy modulates inter-clonal communication among PDLSCs with osteogenic heterogeneity (Fei et al., 2021). Therefore, according to previous evidence, we hypothesized AuNPs have the ability to regulate and control the proliferation and osteogenic differentiation of PDLSCs. The current study investigated the influence of AuNPs on proliferation, osteogenic differentiation and mitophagy of PDLSCs to discover the potential mechanism. The aim of this study is to prove AuNPs improves the proliferation and osteogenic differentiation ability of PDLSCs, possibly due to the activation of mitochondrial autophagy.

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