Liu Zhi, Yang Jianhua, Tan Guodong, Shi Yuanyuan, Tao Dihao, Wang Wenzhe, Li Bei, Jin Fang, He Xiaoning
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 710032, China; State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an 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 710032, China.
Mol Immunol. 2025 Jun;182:83-95. doi: 10.1016/j.molimm.2025.04.005. Epub 2025 Apr 16.
Macrophages are crucial immune cells in periodontal tissues, which play key roles in both the destruction and repair of associated with periodontitis. Targeted modulation of macrophage function has emerged as a potentially effective approach to influence periodontitis progression. This study investigates the effects of methotrexate-loaded extracellular vesicles (MTX-EVs) on inflammatory macrophage polarization both in vivo and in vitro. In a murine periodontitis model, MTX-EVs inhibited alveolar bone resorption, suppressed pro-inflammatory macrophage activation, and promoted anti-inflammatory macrophages. Mechanistically, MTX-EVs reduced acyl-CoA synthetase-1 (ACSL1) expression, which was elevated during inflammation. Inhibition of ACSL1 with triacsin-C in macrophages suppressed the inflammatory phenotype through the promotion of the oxidative phosphorylation (OXPHOS). In contrast, MTX-EVs counteracted the effects of ACSL1 overexpression on macrophage polarization and metabolism. Our findings suggest that targeting ACSL1 via MTX-EVs represents a therapeutic strategy for modulating macrophage polarization and improving periodontitis treatment outcomes.
巨噬细胞是牙周组织中的关键免疫细胞，在与牙周炎相关的组织破坏和修复过程中均发挥着关键作用。靶向调节巨噬细胞功能已成为影响牙周炎进展的一种潜在有效方法。本研究调查了载有甲氨蝶呤的细胞外囊泡（MTX-EVs）在体内和体外对炎性巨噬细胞极化的影响。在小鼠牙周炎模型中，MTX-EVs抑制牙槽骨吸收，抑制促炎性巨噬细胞活化，并促进抗炎性巨噬细胞生成。从机制上讲，MTX-EVs降低了炎症期间升高的酰基辅酶A合成酶-1（ACSL1）的表达。在巨噬细胞中用三辛酰甘油-C抑制ACSL1通过促进氧化磷酸化（OXPHOS）来抑制炎症表型。相反，MTX-EVs抵消了ACSL1过表达对巨噬细胞极化和代谢的影响。我们的研究结果表明，通过MTX-EVs靶向ACSL1代表了一种调节巨噬细胞极化和改善牙周炎治疗效果的治疗策略。
