State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China; State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Disease, Department of Preventive Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
Biochem Biophys Res Commun. 2024 Dec 10;737:150916. doi: 10.1016/j.bbrc.2024.150916. Epub 2024 Oct 28.
Periodontitis is a severe and chronic oral inflammatory disease that leads to the progressive and irreversible destruction of periodontal tissues, ultimately resulting in tooth loss. Among the immune cell subtypes involved, neutrophils play a crucial role in the initiation and progression of periodontitis. Mesenchymal stem cells (MSCs) are essential components of periodontal tissue, contributing to tissue development, homeostasis, and regeneration. Recent studies have demonstrated that neutrophils significantly affect the function of MSCs by changing the inflammatory environment. However, the specific effects of neutrophils on periodontal MSCs during periodontitis remain unclear, highlighting a gap in our understanding of the disease mechanisms. In this study, we utilized the Gli1-CreER;mT/mG transgenic mouse model to specifically mark Gli1 cells, a critical and representative subset of MSCs in the periodontal tissues responsible for maintaining tissue homeostasis. We reveal that neutrophils inhibit the osteogenic differentiation of Gli1 cells and exacerbate alveolar bone destruction by secreting neutrophil extracellular traps (NETs), which induce endoplasmic reticulum stress in Gli1 cells. These findings highlight the pivotal impact of neutrophils on distinct subpopulations of periodontal MSCs in the pathogenesis of periodontitis, offering valuable insights into the underlying mechanisms of the disease and suggesting potential future therapeutic strategies aimed at modulating the interactions between neutrophils and MSCs.
牙周炎是一种严重且慢性的口腔炎症性疾病，可导致牙周组织的进行性和不可逆破坏，最终导致牙齿脱落。在涉及的免疫细胞亚型中，中性粒细胞在牙周炎的发生和发展中起着关键作用。间充质干细胞（MSCs）是牙周组织的重要组成部分，有助于组织发育、稳态和再生。最近的研究表明，中性粒细胞通过改变炎症环境显著影响 MSCs 的功能。然而，中性粒细胞在牙周炎期间对牙周 MSCs 的具体影响尚不清楚，这突显了我们对疾病机制理解的不足。在这项研究中，我们利用 Gli1-CreER;mT/mG 转基因小鼠模型来特异性标记 Gli1 细胞，这是牙周组织中负责维持组织稳态的 MSC 的一个关键和有代表性的亚群。我们揭示中性粒细胞通过分泌中性粒细胞胞外诱捕网（NETs）抑制 Gli1 细胞的成骨分化并加重牙槽骨破坏，导致 Gli1 细胞内质网应激。这些发现强调了中性粒细胞对牙周炎发病机制中不同亚群的牙周 MSC 的关键影响，为该疾病的潜在机制提供了有价值的见解，并提示了潜在的未来治疗策略，旨在调节中性粒细胞和 MSCs 之间的相互作用。
