文献类型：期刊文献

英文题名：Beyond M1/M2: The Pivotal Role of Macrophage Metabolic Reprogramming in Chronic Bone Disease and Targeted Intervention

作者：Wan, Qiao[1];Fang, Zeling[1];Shi, Jiarong[1];Jiang, Yu[2];Jin, Hua[3];Sui, Chuangwei[2];Liu, Xupeng[2];An, Fangyu[4];Zhang, Yanxia[5];Chen, Zhendong[1];Ding, Fan[4];Yan, Chunlu[6]

第一作者：Wan, Qiao

通信作者：An, FY[1];Yan, CL[2]

机构：[1]Gansu Univ Chinese Med, Sch Trad Chinese & Werstern Med, Lanzhou 730000, Peoples R China;[2]Gansu Univ Chinese Med, Sch Basic Med, Lanzhou 730000, Peoples R China;[3]Gansu Univ Chinese Med, Clin Coll Chinese Med, Lanzhou 730000, Peoples R China;[4]Gansu Univ Chinese Med, Teaching Expt Training Ctr, Lanzhou 730000, Peoples R China;[5]Gansu Univ Chinese Med, Sci Res & Expt Ctr, Lanzhou 730000, Peoples R China;[6]Gansu Univ Chinese Med, Natl Inst Dunhuang Med, Lanzhou 730000, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Teaching Expt Training Ctr, Lanzhou 730000, Peoples R China;[2]corresponding author), Gansu Univ Chinese Med, Natl Inst Dunhuang Med, Lanzhou 730000, Peoples R China.|[10735]甘肃中医药大学;

年份：2026

卷号：27

期号：9

外文期刊名：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

收录：;Scopus(收录号：2-s2.0-105038754485);WOS:【SCI-EXPANDED(收录号:WOS:001763634800001)】；

基金：This work was finically supported by the National Natural Science Foundation of China (Grant No. 82560967), Gansu Natural Science Foundation (Grant No. 25JRRA925), the Higher Education Industry Support Program Project of Gansu Province Education Department (Grant No. 2026CYZC-049), University Teacher Innovation Fund Project of Gansu Province Education Department (Grant No. 2026A-119), the Scientific Research Program of Gansu Chinese Medicine Bure (Grant No. GZKG-2024-88), the Graduate "Innovation Star" Project of Gansu Province Education Department (Grant No. 2026CXZX-945), and the Open Fund Project of Key Laboratory of Traditional Chinese Medicine Quality and Standard of Gansu Province (Grant No. ZYZL2025-09).

语种：英文

外文关键词：chronic bone diseases; macrophage polarization; immunometabolism; metabolic reprogramming; bone homeostasis

摘要：The progression of chronic bone diseases is intricately linked to dysregulated macrophage polarisation. However, a comprehensive understanding of the complex interplay between macrophage polarisation and metabolic reprogramming in the context of bone disorders remains elusive. Thus, this review conducted a systematic search of major databases, including PubMed, using combinations of keywords such as "macrophage polarisation," "immunometabolism," "metabolic reprogramming," and "chronic bone diseases" (including "osteoporosis," "osteoarthritis," and "periodontitis"). Inclusion criteria prioritised original research published within the last five years to capture recent advances. Diverging from previous reviews constrained by the classical M1/M2 dichotomy, this article aims to delineate the heterogeneity and functional plasticity of macrophages within the bone microenvironment, emphasising metabolic reprogramming as a central mechanism driving the dynamic behaviour of macrophages across various skeletal pathologies. Furthermore, this review highlights the pivotal roles of specific metabolites-such as succinate, itaconate, and citrate-within the osseous microenvironment, underscoring their influence on macrophage phenotypic transitions and the regulation of bone metabolic homeostasis. Finally, this article envisages innovative therapeutic strategies targeting the "metabolism-immunity axis," encompassing the design of nano-delivery systems to modulate macrophage metabolism, the utilisation of engineered extracellular vesicles, the development of immunometabolism-modulating biomaterials, and the exploration of naturally occurring bioactive molecules. Based on these findings, the present work proposes the "metabolism-immunity-skeleton" axis as a theoretical framework, thereby establishing a robust foundation for the development of precision metabolic immunotherapy tailored to a spectrum of chronic bone diseases.