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类风湿关节炎（Rheumatoid arthritis,RA）是一种以慢性炎症、滑膜增生和进行性骨侵蚀为核心特征的自身免疫性疾病，其高致残率严重影响患者生活质量，其中破骨细胞异常活化是介导骨侵蚀的关键环节。传统研究多聚焦于细胞因子与信号通路对破骨-成骨平衡的调控，而近年来代谢组学与转录组学研究证实，破骨细胞在RA炎症微环境中会发生显著的脂质代谢重编程，从静息状态下依赖葡萄糖的单一代谢模式，转变为葡萄糖代谢、脂肪酸氧化与胆固醇合成协同参与的复合代谢模式，为其持续活化和高耗能骨吸收提供能量与物质支撑。本文梳理了破骨细胞脂质代谢重编程的核心调控机制，包括脂肪酸摄取与转运增强、脂肪酸β-氧化加速、胆固醇代谢异常加强及PRMT6、Dnmt3a介导的表观遗传修饰调控，明确各环节间的协同作用及与RA炎症信号通路（NF-κB、MAPK等）的交互关联；同时总结了靶向脂质代谢重编程关键节点的干预策略，涵盖靶向脂肪酸代谢、胆固醇代谢、表观遗传修饰及上游核心驱动通路（RANKL-RANK、TNF-α）的药物，其中他汀类药物、地诺单抗、抗TNF-α单克隆抗体等已在临床应用中显示出良好潜力。本文通过整合破骨细胞脂质代谢重编程的分子调控网络与靶向干预研究进展，为RA骨侵蚀的精准防治提供理论支撑与新思路。
Abstract：Rheumatoid arthritis(RA) is an autoimmune disease characterized by chronic inflammation, synovial hyperplasia, and progressive bone erosion as its core features. Its high disability rate severely impacts patients' quality of life, among which aberrant activation of osteoclasts represents a critical link mediating bone erosion. Traditional research has primarily focused on the regulation of the osteoclast-osteoblast balance by cytokines and signaling pathways. However, recent metabolomics and transcriptomics studies have confirmed that osteoclasts undergo significant lipid metabolic reprogramming within the inflammatory microenvironment of RA, shifting from a single glucose-dependent metabolic pattern under resting conditions to a composite metabolic pattern involving the synergistic participation of glucose metabolism, fatty acid oxidation, and cholesterol synthesis, thereby providing energy and material support for their sustained activation and energy-consuming bone resorption. This review systematically summarizes the core regulatory mechanisms underlying lipid metabolic reprogramming in osteoclasts, including enhanced fatty acid uptake and transport, accelerated fatty acid β-oxidation, aberrantly upregulated cholesterol metabolism, and epigenetic modifications mediated by PRMT6 and Dnmt3a. It further elucidates the synergistic interactions among these processes and their cross-talk with RA inflammatory signaling pathways(such as NF-κB and MAPK). Additionally, this review summarizes intervention strategies targeting key nodes of lipid metabolic reprogramming, encompassing drugs that target fatty acid metabolism, cholesterol metabolism, epigenetic modifications, and upstream core driving pathways(such as RANKL-RANK and TNF-α). Among these, statins, denosumab, and anti-TNF-α monoclonal antibodies have demonstrated promising potential in clinical applications. By integrating the molecular regulatory network of osteoclast lipid metabolic reprogramming with recent advances in targeted interventions, this review provides theoretical support and novel insights for the precise prevention and treatment of bone erosion in RA.
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基本信息:
中图分类号:R593.22
引用信息:
[1]温金凤,雷桥林,陈辰,等.破骨细胞脂质代谢重编程在类风湿性关节炎骨侵蚀中的作用及靶向干预策略[J].赣南医科大学学报().
2026-06-22
2026-06-22
2026-06-22