2. Academic Validation
  3. Manganese dioxide coupled metal-organic framework as mitophagy regulator alleviates periodontitis through SIRT1-FOXO3-BNIP3 signaling axis

Manganese dioxide coupled metal-organic framework as mitophagy regulator alleviates periodontitis through SIRT1-FOXO3-BNIP3 signaling axis

  • Biomaterials. 2025 Aug:319:123179. doi: 10.1016/j.biomaterials.2025.123179.
Cheng Zhu 1,  Kai Huang 2,  Tiancheng Li 1,  Yixin Li 1,  Yu Jin 1,  Ruomei Li 1,  Zhiyu Zhu 1,  Shengbing Yang 3,  Lunguo Xia 4,  Bing Fang 5
Affiliations

Affiliations

  • 1 Department of Orthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, 200011, China.
  • 2 Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai, 200011, China.
  • 3 Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai, 200011, China. Electronic address: [email protected].
  • 4 Department of Orthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, 200011, China. Electronic address: [email protected].
  • 5 Department of Orthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, 200011, China. Electronic address: [email protected].
PMID: 39983516 DOI: 10.1016/j.biomaterials.2025.123179
Abstract

Periodontitis is a prevalent chronic inflammatory disease characterized by alveolar bone resorption. Its progression is closely linked to oxidative stress where Reactive Oxygen Species (ROS) generated by mitochondria exacerbate inflammation in positive feedback loops. Strategies for mitochondrial regulation hold potential for therapeutic advances. Metal-organic frameworks (MOFs) have shown promise as nanozymes for ROS scavenging. However, inability to directly regulate cellular processes to prevent further ROS production from damaged mitochondria during persistent inflammation makes MOFs insufficient in treating periodontitis. This study synthesizes MnO2@UiO-66(Ce) by introducing MnO2 within nanoscale mesoporous UiO-66 type MOFs. MnO2 coupled with Ce clusters in MOF channels, forms a superoxide dismutase/catalase cascade catalytic system. More importantnly, manganese endows the MOFs with bioactive effects which enhances Mitophagy, facilitating the removal of damaged mitochondria, thereby restoring long-term cellular homeostasis. The results demonstrate that this synergistic antioxidant solution MnO2@UiO-66 restores mitochondrial homeostasis and osteogenic activity of periodontal ligament cells in vitro and alleviates inflammatory bone resorption in a ligature-induced periodontitis model in vivo. The SIRT1-FOXO3-BNIP3 signaling axis plays a key role in this process. This study may provide a design strategy that combines a highly efficient cascade catalytic system with long-term regulation of cellular homeostasis to combat oxidative stress in chronic inflammation.

Keywords

Metal-organic frameworks; Mitophagy; Oxidative stress; Periodontitis.

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