Tang Hui, Zhou Yi, Ma Lu, Ye Yu, Xiao Qian-Xuan, Tang Jing-Qi, Xu Yan
Department of Periodontology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China; State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China.
Department of Periodontology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China; State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, Nanjing, China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China.
Free Radic Biol Med. 2025 Feb 1;227:407-419. doi: 10.1016/j.freeradbiomed.2024.11.033. Epub 2024 Nov 16.
Diabetes-associated periodontitis (DP) is recognized as an inflammatory disease that can lead to teeth loss. Uncontrolled chronic low-grade inflammation-induced senescence impairs the stemness of human periodontal stem cells (hPDLSCs). Sirtuin 3 (SIRT3), an NAD-dependent deacetylase, is pivotal in various biological processes and is closely linked to aging and aging-related diseases. This study aims to explore the mechanism of SIRT3-related senescence and osteogenic differentiation of hPDLSCs under DP and explored the novelty therapeutic targets. Our study revealed that SIRT3 expression was markedly inhibited in periodontal ligament stem cells (PDLSCs) stimulated by high glucose and lipopolysaccharide. Both in vitro and in vivo, reduced SIRT3 expression accelerated cell senescence and impaired osteogenic differentiation of hPDLSCs. We demonstrated that SIRT3 binds to and deacetylates leucine-rich pentatricopeptide repeat-containing protein (LRPPRC), thereby modulating senescence. Additionally, we found that LRPPRC regulates senescence by modulating oxidative phosphorylation and oxidative stress. The activation of SIRT3 by honokiol significantly delayed senescence and promoted alveolar bone regeneration in mice after DP. Our findings indicate that the activation of SIRT3 negatively regulates hPDLSCs senescence by deacetylating LRPPRC, suggesting SIRT3 as a promising therapeutic target for DP.
糖尿病相关性牙周炎（DP）被认为是一种可导致牙齿脱落的炎症性疾病。不受控制的慢性低度炎症诱导的衰老会损害人牙周膜干细胞（hPDLSCs）的干性。沉默调节蛋白3（SIRT3）是一种依赖烟酰胺腺嘌呤二核苷酸的脱乙酰酶，在各种生物学过程中起关键作用，并且与衰老及衰老相关疾病密切相关。本研究旨在探讨DP条件下SIRT3相关的hPDLSCs衰老和成骨分化机制，并探索新的治疗靶点。我们的研究表明，在高糖和脂多糖刺激的牙周膜干细胞（PDLSCs）中，SIRT3表达明显受到抑制。在体外和体内，SIRT3表达降低均加速了hPDLSCs的细胞衰老并损害其成骨分化。我们证明SIRT3与富含亮氨酸的五肽重复序列蛋白（LRPPRC）结合并使其去乙酰化，从而调节衰老。此外，我们发现LRPPRC通过调节氧化磷酸化和氧化应激来调节衰老。厚朴酚激活SIRT3可显著延缓DP后小鼠的衰老并促进牙槽骨再生。我们的研究结果表明，SIRT3的激活通过使LRPPRC去乙酰化来负向调节hPDLSCs衰老，提示SIRT3是DP的一个有前景的治疗靶点。
