摘要
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.关键词
类风湿性关节炎/破骨细胞/脂质代谢重编程/骨侵蚀/信号通路/靶向治疗Key words
Rheumatoid arthritis/Osteoclast/Lipid metabolism reprogramming/Bone erosion/Signaling pathway/Targeted therapy分类
医药卫生
