切换至 "中华医学电子期刊资源库"
高级检索
中华关节外科杂志(电子版)

中华关节外科杂志(电子版) ›› 2025, Vol. 19 ›› Issue (03) : 336 -342. doi: 10.3877/cma.j.issn.1674-134X.2025.03.011

综述

微循环对巨噬细胞影响在激素性股骨头坏死机制探究
张兆坤1,2, 赵俊杰1,2, 黄鹏飞1,2, 王玺玉1,2, 赵宇昊1,2, 赵海燕2,1,†()   
  1. 1730000　兰州大学第一临床医学院
    2730000　兰州大学第一医院骨科
  • 收稿日期:2024-10-27 出版日期:2025-06-01
  • 通信作者: 赵海燕
  • 基金资助:
    国家自然科学基金项目(82060394); 兰州市人才创新创业项目(2020-RC-45); 兰州大学第一医院院内基金(ldyyyn2022-73)

Mechanism investigation of influence of microcirculation on macrophages in steroid-induced femoral head necrosis

Zhaokun Zhang1,2, Junjie Zhao1,2, Pengfei Huang1,2, Xiyu Wang1,2, YuHao Zhao1,2, Haiyan Zhao2,1,†()   

  1. 1The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China
    2Department of Orthopaedics, the First Hospital of Lanzhou University, Lanzhou 730000, China
  • Received:2024-10-27 Published:2025-06-01
  • Corresponding author: Haiyan Zhao
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

张兆坤, 赵俊杰, 黄鹏飞, 王玺玉, 赵宇昊, 赵海燕. 微循环对巨噬细胞影响在激素性股骨头坏死机制探究[J/OL]. 中华关节外科杂志(电子版), 2025, 19(03): 336-342.

Zhaokun Zhang, Junjie Zhao, Pengfei Huang, Xiyu Wang, YuHao Zhao, Haiyan Zhao. Mechanism investigation of influence of microcirculation on macrophages in steroid-induced femoral head necrosis[J/OL]. Chinese Journal of Joint Surgery(Electronic Edition), 2025, 19(03): 336-342.

激素性股骨头坏死（SONFH）是一种临床常见代谢性疾病，然而对其发病机制的研究有多种理论学说，但目前认为微循环障碍是引起股骨头坏死主要病理机制。而巨噬细胞作为一种免疫细胞，正常情况下在调节组织微环境平衡具有重要作用。然而，微循环障碍后生理环境的变化影响其代谢状态的变换而出现高异质性和可塑性。特别是起病早期，血管生长因子串扰巨噬细胞代谢对骨吸收和骨重塑的影响，在很大程度上仍然难以捉摸。因此，探究微循环障碍后分泌的相关血管生长因子在介导骨免疫细胞对激素性股骨头坏死发病机制具有潜在价值。

关键词: 巨噬细胞, 微循环, 稳态

Steroid induced osteonecrosis of the femoral head (SONFH) is a common metabolic disease in clinical practice. However, there are multiple theoretical theories on its pathogenesis, but it is currently believed that microcirculation disorders are the main pathological mechanism causing osteonecrosis of the femoral head. As an immune cell, macrophages play an important role in regulating the balance of tissue microenvironment under normal circumstances. However, the changes in physiological environment after microcirculatory disorders affect the transformation of their metabolic status, resulting in high heterogeneity and plasticity. Especially in the early stages of onset, the impact of vascular growth factor interference on macrophage metabolism on bone resorption and remodeling remains largely elusive. Therefore, investigating the vascular growth factors secreted following microcirculatory disturbances has potential significance in elucidating their role in mediating the pathogenesis of steroid-induced femoral head necrosis via bone immune cells.

Key words: Macrophage, Microcirculation, Homeostasis
图1 影响巨噬细胞表型转化相关因子
Figure 1 Factors involved in regulating macrophage phenotype transformation
[1]
赵德伟. 加强对股骨头缺血性坏死病理生理的认识[J/CD].中华关节外科杂志（电子版）, 2014, 8（05）: 560-562.
[2]
Zhang QY, Li ZR, Gao FQ, et al. Pericollapse stage of osteonecrosis of the femoral head: a last chance for joint preservation[J]. Chin Med J, 2018, 131（21）: 2589-2598.
[3]
Ma M, Tan Z, Li W, et al. Osteoimmunology and osteonecrosis of the femoral head[J]. Bone Joint Res, 2022, 11（1）: 26-28.
[4]
Weivoda MM, Bradley EW. Macrophages and bone remodeling[J]. J Bone Miner Res, 2023, 38（3）: 359-369.
[5]
Mehla K, Singh PK. Metabolic regulation of macrophage polarization in cancer[J]. Trends Cancer, 2019, 5（12）: 822-834.
[6]
Yue C, Cui G, Cheng Y, et al. Aucubin suppresses TLR4/NF-κBsignalling to shift macrophages toward M2 phenotype in glucocorticoid-associated osteonecrosis of the femoral head[J/OL]. J Cell Mol Med, 2024, 28 （15）: e18583. DOI:10.1111/jcmm.18583.
[7]
Spiller KL, Anfang RR, Spiller KJ, et al. The role of macrophage phenotype in vascularization of tissue engineering scaffolds[J]. Biomaterials, 2014, 35（15）: 4477-4488.
[8]
Cheng Y, Chen H, Duan P, et al. Early depletion of M1 macrophages retards the progression of glucocorticoid-associated osteonecrosis of the femoral head[J/OL]. Int Immunopharmacol, 2023, 122: 110639. DOI:10.1016/j.intimp.2023.110639.
[9]
Adapala NS, Kim HKW. Comprehensive genome-wide transcriptomic analysis of immature articular cartilage following ischemic osteonecrosis of the femoral head in piglets[J/OL]. PLoS One, 2016, 11（4）: e0153174. DOI:10.1371/journal.pone.0153174.
[10]
Tan Z, Wang Y, Chen Y, et al. The dynamic feature of macrophage M1/M2 imbalance facilitates the progression of non-traumatic osteonecrosis of the femoral head [J/OL]. Front Bioeng Biotechnol, 2022, 10: 912133. DOI:10.3389/fbioe.2022.912133.
[11]
Li W, Sakai T, Nishii T, et al. Distribution of TRAP-positive cells and expression of HIF-1alpha, VEGF, and FGF-2 in the reparative reaction in patients with osteonecrosis of the femoral head[J]. J Orthop Res, 2009, 27（5）: 694-700.
[12]
Wang C, Wang X, Xu XL, et al. Bone microstructure and regional distribution of osteoblast and osteoclast activity in the osteonecrotic femoral head[J/OL]. PLoS One, 2014, 9（5）: e96361. DOI:10.1371/journal.pone.0096361.
[13]
Ikeuchi K, Hasegawa Y, Seki T, et al. Epidemiology of nontraumatic osteonecrosis of the femoral head in Japan[J]. Mod Rheumatol, 2015, 25（2）: 278-281.
[14]
Ren G, Han J, Mo J, et al. Differential gene expression and immune cell infiltration in patients with steroid-induced necrosis of the femoral head[J]. Endocr Metab Immune Disord Drug Targets, 2024, 24（12）: 1377-1394.
[15]
Adapala NS, Yamaguchi R, Phipps M, et al. Necrotic bone stimulates proinflammatory responses in macrophages through the activation of toll-like receptor 4 [J]. Am J Pathol, 2016, 186（11）: 2987-2999.
[16]
Pei J, Fan L, Nan K, et al. Excessive activation of TLR4/NF-κB interactively suppresses the canonical Wnt/β-catenin pathway and induces SANFH in SD rats [J/OL]. Sci Rep, 2017, 7（1）: 11928. DOI:10.1038/s41598-017-12196-8.
[17]
Tian L, Wen Q, Dang X, et al. Immune response associated with Toll-like receptor 4 signaling pathway leads to steroid-induced femoral head osteonecrosis [J/OL]. BMC Musculoskelet Disord, 2014, 15: 18. DOI:10.1186/1471-2474-15-18.
[18]
Willenborg S, Lucas T, van Loo G, et al. CCR2 recruits an inflammatory macrophage subpopulation critical for angiogenesis in tissue repair [J]. Blood, 2012, 120（3）: 613-625.
[19]
Shinohara I, Tsubosaka M, Toya M, et al. C-C motif chemokine ligand 2 enhances macrophage chemotaxis, osteogenesis, and angiogenesis during the inflammatory phase of bone regeneration[J/OL]. Biomolecules, 2023, 13（11）: 1665. DOI:10.3390/biom13111665.
[20]
Shi C, Jia T, Mendez-Ferrer S, et al. Bone marrow mesenchymal stem and progenitor cells induce monocyte emigration in response to circulating toll-like receptor ligands [J]. Immunity, 2011, 34（4）: 590-601.
[21]
Sucur A, Jajic Z, Artukovic M, et al. Chemokine signals are crucial for enhanced homing and differentiation of circulating osteoclast progenitor cells [J/OL]. Arthritis Res Ther, 2017, 19（1）: 142. DOI:10.1186/s13075-017-1337-6.
[22]
Peng Y, Wu S, Li Y, et al. Type H blood vessels in bone modeling and remodeling [J]. Theranostics, 2020, 10（1）: 426-436.
[23]
Ma T, Wang Y, Ma J, et al. Research progress in the pathogenesis of hormone-induced femoral head necrosis based on microvessels: a systematic review [J/OL]. J Orthop Surg Res, 2024, 19（1）: 265. DOI:10.1186/s13018-024-04748-2.
[24]
Lobov I, Mikhailova N. The role of Dll4/Notch signaling in normal and pathological ocular angiogenesis: Dll4 controls blood vessel sprouting and vessel remodeling in normal and pathological conditions [J/OL]. J Ophthalmol, 2018, 2018: 3565292. DOI:10.1155/2018/3565292.
[25]
Tiemeijer LA, Frimat JP, Stassen OA, et al. Spatial patterning of the Notch ligand Dll4 controls endothelial sprouting in vitro[J/OL]. Sci Rep, 2018, 8（1）: 6392. DOI:10.1038/s41598-018-24646-y.
[26]
Hu Y, Li H. DLL4/Notch blockade disrupts mandibular advancement-induced condylar osteogenesis by inhibiting H-type angiogenesis [J]. J Oral Rehabil, 2024, 51（4）: 754-761.
[27]
Li L, Jin JH, Liu HY, et al. Notch1 signaling contributes to TLR4-triggered NF-κB activation in macrophages [J/OL]. Pathol Res Pract, 2022, 234: 153894. DOI:10.1016/j.prp.2022.153894.
[28]
Pagie S, Gérard N, Charreau B. Notch signaling triggered via the ligand DLL4 impedes M2 macrophage differentiation and promotes their apoptosis [J/OL]. Cell Commun Signal, 2018, 16（1）: 4. DOI:10.1186/s12964-017-0214-x.
[29]
Wu D, Xu J, Jiao W, et al. Suppression of macrophage activation by sodium danshensuvia HIF-1α/STAT3/NLRP3 pathway ameliorated collagen-induced arthritis in mice [J/OL]. Molecules, 2023, 28（4）: 1551. DOI:10.3390/molecules28041551.
[30]
Christofides A, Strauss L, Yeo A, et al. The complex role of tumor-infiltrating macrophages [J]. Nat Immunol, 2022, 23（8）: 1148-1156.
[31]
Marrocco A, Ortiz LA. Role of metabolic reprogramming in pro-inflammatory cytokine secretion from LPS or silica-activated macrophages[J/OL]. Front Immunol, 2022, 13: 936167. DOI:10.3389/fimmu.2022.936167.
[32]
Palsson-McDermott EM, Curtis AM, Goel G, et al. Pyruvate kinase M2 regulates hif-1α activity and IL-1β induction and is a critical determinant of the Warburg effect in LPS-activated macrophages[J/OL]. Cell Metab, 2015, 21（2）: 347. DOI:10.1016/j.cmet.2015.01.017.
[33]
Jha AK, Huang SC, Sergushichev A, et al. Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization[J]. Immunity, 2015, 42（3）: 419-430.
[34]
Tannahill GM, Curtis AM, Adamik J, et al. Succinate is an inflammatory signal that induces IL-1β through HIF-1α[J]. Nature, 2013, 496（7444）: 238-242.
[35]
Shirai T, Nazarewicz RR, Wallis BB, et al. The glycolytic enzyme PKM2 bridges metabolic and inflammatory dysfunction in coronary artery disease[J]. J Exp Med, 2016, 213（3）: 337-354.
[36]
Liang J, Cao R, Zhang Y, et al. PKM2 dephosphorylation by Cdc25A promotes the Warburg effect and tumorigenesis[J/OL]. Nat Commun, 2016, 7: 12431. DOI:10.1038/ncomms12431.
[37]
Das Gupta K, Shakespear MR, Curson JEB, et al. Class IIa histone deacetylases drive toll-like receptor-inducible glycolysis and macrophage inflammatory responses via pyruvate kinase M2[J]. Cell Rep, 2020, 30（8）: 2712-2728.e8.
[38]
Xu J, Jiang C, Wang X, et al. Upregulated PKM2 in macrophages exacerbates experimental arthritis via STAT1 signaling[J]. J Immunol, 2020, 205（1）: 181-192.
[39]
Zhang Y, Zhu L, Li X, et al. M2 macrophage exosome-derived lncRNA AK083884 protects mice from CVB3-induced viral myocarditis through regulating PKM2/HIF-1α axis mediated metabolic reprogramming of macrophages[J/OL]. Redox Biol, 2024, 69: 103016. DOI:10.1016/j.redox.2023.103016.
[40]
Verdegem D, Moens S, Stapor P, et al. Endothelial cell metabolism: parallels and divergences with cancer cell metabolism[J/OL]. Cancer Metab, 2014, 2: 19. DOI:10.1186/2049-3002-2-19.
[41]
Wu H, He L, Shi J, et al. Resveratrol inhibits VEGF-induced angiogenesis in human endothelial cells associated with suppression of aerobic glycolysis via modulation of PKM2 nuclear translocation[J]. Clin Exp Pharmacol Physiol, 2018, 45（12）: 1265-1273.
[42]
Li F, Liu X, Li M, et al. Inhibition of PKM2 suppresses osteoclastogenesis and alleviates bone loss in mouse periodontitis[J/OL]. IntImmunopharmacol, 2024, 129: 111658. DOI:10.1016/j.intimp.2024.111658.
[43]
Guo J, Ren R, Yao X, et al. PKM2 suppresses osteogenesis and facilitates adipogenesis by regulating β-catenin signaling and mitochondrial fusion and fission[J]. Aging, 2020, 12（4）: 3976-3992.
[44]
ZengW, XingZ, Tan M, et al. Propofolregulatesactivatedmacrophagesmetabolismthroughinhibition of ROS-mediatedGLUT1 expression[J]. Inflamm Res, 2021, 70（4）: 473-481.
[46]
Freemerman AJ, Johnson AR, Sacks GN, et al. Metabolic reprogramming of macrophages: glucose transporter 1 （GLUT1）-mediated glucose metabolism drives a proinflammatoryphenotype[J]. J Biol Chem, 2014, 289（11）: 7884-7896.
[47]
Wang X, Tang M, Zhang Y, et al. Dexamethasone enhances glucose uptake by SGLT1 and GLUT1 and boosts ATP generation through the PPP-TCA cycle in bovine neutrophils[J/OL]. J Vet Sci, 2022, 23（5）: e76. DOI:10.4142/jvs.22112.
[48]
Wang Q, Nie L, Zhao P, et al. Diabetes fuels periodontal lesions via GLUT1-driven macrophage inflammaging[J/OL]. Int J Oral Sci, 2021, 13（1）: 11. DOI:10.1038/s41368-021-00116-6.
[49]
Torrente L, DeNicola GM. GAPDH redox redux-rewiring pentose phosphate flux[J]. Nat Metab, 2023, 5（4）: 538-539.
[50]
Weng W, Zhang Y, Gui L, et al. PKM2 promotes proinflammatory macrophage activation in ankylosing spondylitis[J]. J Leukoc Biol, 2023, 114（6）: 595-603.
[51]
Shao C, Lin S, Liu S, et al. HIF1α-induced glycolysis in macrophage is essential for the protective effect of ouabain during endotoxemia[J/OL]. Oxid Med Cell Longev, 2019, 2019: 7136585. DOI:10.1155/2019/7136585.
[52]
Hu Y, Lou X, Wang R, et al. Aspirin, a potential GLUT1 inhibitor in a vascular endothelial cell line[J]. Open Med, 2019, 14: 552-560.
[53]
Mamun AA, Hayashi H, Yamamura A, et al. Hypoxia induces the translocation of glucose transporter 1 to the plasma membrane in vascular endothelial cells[J/OL]. J Physiol Sci, 2020, 70（1）: 44. DOI:10.1186/s12576-020-00773-y.
[54]
Luo H, Wei J, Wu S, et al. Elucidating the role of the GC/GR/GLUT1 axis in steroid-induced osteonecrosis of the femoral head: a proteomic approach[J/OL]. Bone, 2024, 183: 117074. DOI:10.1016/j.bone.2024.117074.
[55]
Zhou HC, Yu WW, Yan XY, et al. Lactate-driven macrophage polarization in the inflammatory microenvironment alleviates intestinal inflammation[J/OL]. Front Immunol, 2022, 13: 1013686. DOI:10.3389/fimmu.2022.1013686.
[56]
Wang J, Yang P, Yu T, et al. Lactylation of PKM2 suppresses inflammatory metabolic adaptation in pro-inflammatory macrophages[J]. Int J BiolSci, 2022, 18（16）: 6210-6225.
[57]
Zhao Y, Zhao B, Wang X, et al. Macrophage transcriptome modification induced by hypoxia and lactate[J]. Exp Ther Med, 2019, 18（6）: 4811-4819.
[58]
Murphy MP, O’Neill LAJ. Krebs cycle reimagined: the emerging roles of succinate and itaconate as signal transducers[J]. Cell, 2018, 174（4）: 780-784.
[59]
Shi W, Cassmann TJ, Bhagwate AV, et al. Lactic acid induces transcriptional repression of macrophage inflammatory response via histone acetylation[J/OL]. Cell Rep, 2024, 43（2）: 113746. DOI:10.1016/j.celrep.2024.113746.
[60]
Alavi MS, Memarpour S, Pazhohan-Nezhad H, et al. Applications of poly（lactic acid） in bone tissue engineering: a review article[J]. Artif Organs, 2023, 47（9）: 1423-1430.
[61]
Wu J, Hu M, Jiang H, et al. Endothelial cell-derived lactate triggers bone mesenchymal stem cell histone lactylation to attenuate osteoporosis[J/OL]. Adv Sci, 2023, 10（31）: e2301300. DOI:10.1002/advs.202301300.
[62]
Zhang J, Muri J, Fitzgerald G, et al. Endothelial lactate controls muscle regeneration from ischemia by inducing M2-like macrophage polarization[J]. Cell Metab, 2020, 31（6）: 1136-1153.e7.
[1] 张霞, 冯娅娆, 罗寰, 杨金良, 张斌, 郑学军. 尪痹胶囊联合来氟米特对类风湿关节炎炎症指标的影响[J/OL]. 中华关节外科杂志(电子版), 2025, 19(01): 55-64.
[2] 张凯, 乔永杰, 林志强, 刘健, 邓泽群, 谭飞, 曾健康, 李嘉欢, 李培杰, 周胜虎. 假体周围骨溶解中巨噬细胞极化的机制研究进展[J/OL]. 中华关节外科杂志(电子版), 2024, 18(05): 618-625.
[3] 杨瑾, 刘雪克, 张媛媛, 金钧, 韦瑶. 肠道微生物来源石胆酸对脓毒症相关肝损伤的保护作用[J/OL]. 中华危重症医学杂志(电子版), 2024, 17(04): 265-274.
[4] 鲁嘉懿, 唐菲, 卢芬, 陶于洪. 儿童系统性红斑狼疮相关性急性胰腺炎的临床诊疗及预后分析[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(06): 635-643.
[5] 黄洲龙, 张金丽, 周日兴, 于昊, 张志. 巨噬细胞向肌成纤维细胞转分化在纤维化疾病中作用的研究进展[J/OL]. 中华损伤与修复杂志(电子版), 2025, 20(03): 271-275.
[6] 陈浩, 林梁, 邹来宾, 郭胜蓝. 成石饮食诱发胆结石及肝损伤机制的研究[J/OL]. 中华普通外科学文献(电子版), 2025, 19(01): 42-47.
[7] 刘洪千, 马琦, 陈娟娟, 王成军, 武玲玲, 冯喜英. miR-150-5p 在青海地区结核分枝杆菌感染患者血清中的表达及意义[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(01): 42-47.
[8] 马苗苗, 次苗苗, 寇振宇, 王斌锋, 和建武. 儿童急性下呼吸道感染血清hBD-2、MIP-1α、IL-13 与病情严重程度的临床分析[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(06): 1008-1012.
[9] 向青, 龚道辉, 赵才林, 张硕辛, 秦蘅, 刘禹. 巨噬细胞参与免疫调节机制在肺动脉高压中的影响及相关纳米材料的研究进展[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(06): 1027-1030.
[10] 张天麒, 宾晓芸. 阿托伐他汀对高脂饮食诱导的新西兰兔代谢功能障碍相关脂肪性肝病中巨噬细胞极化的作用及机制研究[J/OL]. 中华细胞与干细胞杂志(电子版), 2025, 15(03): 167-178.
[11] 朱军, 宋家伟, 乔一桓, 郭雅婕, 刘帅, 姜玉, 李纪鹏. M2型巨噬细胞特征基因与结肠癌免疫微环境研究[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(04): 303-311.
[12] 张鹏飞, 王雯. 肌肉因子对骨骼调控作用的研究进展[J/OL]. 中华老年骨科与康复电子杂志, 2024, 10(06): 372-378.
[13] 张笑闻, 李菁, 管生, 范梦妍, Mateus TN Mach, 万佳鑫, 林日金, 刘爱华, 王蕾, 张志科. 脑动脉瘤光学相干断层扫描表现二例[J/OL]. 中华介入放射学电子杂志, 2025, 13(01): 93-96.
[14] 何玉花, 钟欢妹, 王文惠, 沈永棋, 刘映云, 顾国威, 陈丹娜. 不同表型多囊卵巢综合征患者代谢指标及肥胖相关指标对多囊卵巢综合征合并代谢综合征人群的诊断效能分析[J/OL]. 中华临床实验室管理电子杂志, 2024, 12(04): 212-220.
[15] 冯欣, 尤素伟, 史晓梅, 王相斌, 巩巧丽, 王俊英. 血清VEGF-A、HIF-1α、MIF水平与急性脑梗死并发脑心综合征的关联性研究[J/OL]. 中华脑血管病杂志(电子版), 2025, 19(03): 213-219.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号

AI
小
编
AI小编
你好！我是《中华医学电子期刊资源库》AI小编，有什么可以帮您的吗？