Liu Hongrui, Sun Changyun, Jiang Yujun, Gao Ruihan, Ying Qiaohui, Li Xiaolin, Liu Hongrui, Guo Jie, Li Minqi
Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No.44-1 Wenhua Road West, 250012, Jinan, Shandong, China; Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No.44-1 Wenhua Road West, 250012, Jinan, Shandong, China; Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, China.
Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No.44-1 Wenhua Road West, 250012, Jinan, Shandong, China; Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, China.
Int Immunopharmacol. 2025 Jan 27;146:113894. doi: 10.1016/j.intimp.2024.113894. Epub 2024 Dec 26.
Diabetes exacerbates the occurrence and severity of periodontitis, the pathogenesis of diabetic periodontitis (DPD) is influenced by the delayed resolution of inflammation. Eldecalcitol (ED-71) has shown promise in preventing bone loss in DPD. We herein aimed to investigate the role of ED-71 in the inflammatory regression phase of DPD and elucidate the underlying mechanisms. Type-2 diabetes was induced by streptozotocin injection in Wistar rats, and to explore the in vivo effect of ED-71 on macrophage efferocytosis, periodontitis was induced by ligation combined with lipopolysaccharide. Alveolar bone destruction was assessed using micro-computed tomography, hematoxylin-eosin, immunohistochemistry, and tartrate-resistant acid phosphatase staining. Immunofluorescence staining and flow cytometry detected neutrophils, apoptotic cells, and macrophage polarization in periodontal tissue. Additionally, flow cytometry, real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay were used to examine macrophage efferocytosis and changes in store-operated calcium entry (SOCE). We found that rats with diabetes exhibited more severe alveolar bone destruction and increased neutrophil aggregates in periodontal tissue. Following the ED-71 administration, alveolar bone loss significantly decreased, and the immune microenvironment of periodontal tissue tended to suppress inflammation. Macrophages stimulated with high glucose experienced disruption of SOCE machinery, leading to the inhibition of efferocytosis in vitro. ED-71 demonstrated the ability to restore macrophage efferocytosis by correcting SOCE, and preventing sustained inflammatory damage to periodontal tissue. In conclusion, diabetes impairs macrophage efferocytosis and M2 polarization in periodontitis rats, resulting in the delayed resolution of inflammation. ED-71 could attenuate alveolar bone loss by mitigating macrophage via SOCE machinery in DPD.
糖尿病会加剧牙周炎的发生和严重程度，糖尿病性牙周炎（DPD）的发病机制受炎症消退延迟的影响。 eldecalcitol（ED-71）在预防DPD中的骨质流失方面已显示出前景。我们在此旨在研究ED-71在DPD炎症消退阶段的作用，并阐明其潜在机制。通过向Wistar大鼠注射链脲佐菌素诱导2型糖尿病，为了探究ED-71对巨噬细胞吞噬作用的体内影响，通过结扎联合脂多糖诱导牙周炎。使用显微计算机断层扫描、苏木精-伊红染色、免疫组织化学和抗酒石酸酸性磷酸酶染色评估牙槽骨破坏情况。免疫荧光染色和流式细胞术检测牙周组织中的中性粒细胞、凋亡细胞和巨噬细胞极化。此外，使用流式细胞术、实时聚合酶链反应、蛋白质印迹法和酶联免疫吸附测定来检测巨噬细胞吞噬作用和储存-操作性钙内流（SOCE）的变化。我们发现糖尿病大鼠表现出更严重的牙槽骨破坏，并且牙周组织中的中性粒细胞聚集增加。给予ED-71后，牙槽骨丢失显著减少，并且牙周组织的免疫微环境倾向于抑制炎症。高糖刺激的巨噬细胞经历了SOCE机制的破坏，导致体外吞噬作用受到抑制。ED-71通过纠正SOCE表现出恢复巨噬细胞吞噬作用的能力，并防止对牙周组织的持续炎症损伤。总之，糖尿病损害了牙周炎大鼠的巨噬细胞吞噬作用和M2极化，导致炎症消退延迟。ED-71可以通过在DPD中经由SOCE机制减轻巨噬细胞作用来减轻牙槽骨丢失。
