异位骨化中巨噬细胞的糖代谢重编程

Abstract

Abstract: Heterotopic ossification (HO) was the formation of bone outside the skeleton in non bone tissue. Inflammation had a contributory role in the development of HO, and macrophages were key mediators of inflammation. Large numbers of macrophages were recruited to the site of HO and were involved in the molecular mechanisms of osteogenic differentiation of mesenchymal stem cells, angiogenesis, and the hypoxic microenvironment. Influenced by changes in the microenvironment, macrophages were activated and polarized into different subpopulations exercising different functions. Metabolites of the tricarboxylic acid cycle played specific roles for both macrophage activation and homeostatic functions. In this paper, we provided an overview of the reprogramming of glycometabolism in macrophages in HO.

Key words: heterotopic ossification, macrophages, glucose metabolism reprogramming, glycolysis, tricarboxylic acid cycle

References 60

[1]	HWANG C D, PAGANI C A, NUNEZ J H, et al. Contemporary perspectives on heterotopic ossification[J/OL]. JCI insight, 2022, 7(14): e158996. DOI:10.1172/jci.insight.158996.
[2]	Lawand J, Loeffelholz Z, Khurshid B, Barcak E. Heterotopic Ossification after Trauma. Orthop Clin North Am. 2023 Jan;54(1):37-46. doi: 10.1016/j.ocl.2022.08.007. PMID: 3609. 4025
[3]	ZHAO Y, OUYANG N, CHEN L, et al. Stimulating Factors and Origins of Precursor Cells in Traumatic Heterotopic Ossification Around the Temporomandibular Joint in Mice[J/OL]. Frontiers in Cell and Developmental Biology, 2020, 8: 445. DOI:10.3389/fcell.2020.00445.
[4]	Ravazzolo R, Bocciardi R. Genomic Context and Mechanisms of the ACVR1 Mutation in Fibrodysplasia Ossificans Progressiva. Biomedicines. 2021 Feb 5;9(2):154. doi: 10.3390/biomedicines9020154. PMID: 33562470; PMCID: PMC7914827..
[5]	KAPLAN F S, AL MUKADDAM M, STANLEY A, et al. Fibrodysplasia ossificans progressiva (FOP): A disorder of osteochondrogenesis[J/OL]. Bone, 2020, 140: 115539. DOI:10.1016/j.bone.2020.115539.
[6]	MEYERS C, LISIECKI J, MILLER S, et al. Heterotopic Ossification: A Comprehensive Review[J/OL]. JBMR plus, 2019, 3(4): e10172. DOI:10.1002/jbm4.10172.
[7]	KAPLAN F S, SHORE E M. Progressive osseous heteroplasia[J/OL]. Journal of Bone and Mineral Research: The Official Journal of the American Society for Bone and Mineral Research, 2000, 15(11): 2084-2094. DOI:10.1359/jbmr.2000.15.11.2084.
[8]	MEDZHITOV R. Origin and physiological roles of inflammation[J/OL]. Nature, 2008, 454(7203): 428-435. DOI:10.1038/nature07201.
[9]	Hwang CD, Pagani CA, Nunez JH, et al. Contemporary perspectives on heterotopic ossification. JCI Insight. 2022 Jul 22;7(14):e158996. doi: 10.1172/jci.insight.158996. PMID: 35866484; PMCID: PMC9431693.
[10]	QURESHI A T, CRUMP E K, PAVEY G J, et al. Early Characterization of Blast-related Heterotopic Ossification in a Rat Model[J/OL]. Clinical Orthopaedics and Related Research, 2015, 473(9): 2831-2839. DOI:10.1007/s11999-015-4240-y.
[11]	XU Y, HUANG M, HE W, et al. Heterotopic Ossification: Clinical Features, Basic Researches, and Mechanical Stimulations[J/OL]. Frontiers in Cell and Developmental Biology, 2022, 10: 770931. DOI:10.3389/fcell.2022.770931.
[12]	AGARWAL S, LODER S, BROWNLEY C, et al. Inhibition of Hif1α prevents both trauma-induced and genetic heterotopic ossification[J/OL]. Proceedings of the National Academy of Sciences of the United States of America, 2016, 113(3): E338-347. DOI:10.1073/pnas.1515397113.
[13]	LU G, TANDANG-SILVAS M R, DAWSON A C, et al. Hypoxia-selective allosteric destabilization of activin receptor-like kinases: A potential therapeutic avenue for prophylaxis of heterotopic ossification[J/OL]. Bone, 2018, 112: 71-89. DOI:10.1016/j.bone.2018.03.027.
[14]	BRADY R D, SHULTZ S R, MCDONALD S J, et al. Neurological heterotopic ossification: Current understanding and future directions[J/OL]. Bone, 2018, 109: 35-42. DOI:10.1016/j.bone.2017.05.015.
[15]	ALEXANDER K A, TSENG H W, FLEMING W, et al. Inhibition of JAK1/2 Tyrosine Kinases Reduces Neurogenic Heterotopic Ossification After Spinal Cord Injury[J/OL]. Frontiers in Immunology, 2019, 10: 377. DOI:10.3389/fimmu.2019.00377.
[16]	DE SOUZA P P C, HENNING P, LERNER U H. Stimulation of Osteoclast Formation by Oncostatin M and the Role of WNT16 as a Negative Feedback Regulator[J/OL]. International Journal of Molecular Sciences, 2022, 23(6): 3287. DOI:10.3390/ijms23063287.
[17]	CHAKKALAKAL S A, ZHANG D, CULBERT A L, et al. An Acvr1 R206H knock-in mouse has fibrodysplasia ossificans progressiva[J/OL]. Journal of Bone and Mineral Research: The Official Journal of the American Society for Bone and Mineral Research, 2012, 27(8): 1746-1756. DOI:10.1002/jbmr.1637.
[18]	BARRUET E, MORALES B M, CAIN C J, et al. NF-κB/MAPK activation underlies ACVR1-mediated inflammation in human heterotopic ossification[J/OL]. JCI insight, 2018, 3(22): 122958. DOI:10.1172/jci.insight.122958.
[19]	WANG H, LINDBORG C, LOUNEV V, et al. Cellular Hypoxia Promotes Heterotopic Ossification by Amplifying BMP Signaling[J/OL]. Journal of Bone and Mineral Research: The Official Journal of the American Society for Bone and Mineral Research, 2016, 31(9): 1652-1665. DOI:10.1002/jbmr.2848.
[20]	Chazaud B, Sonnet C, Lafuste P, et al.Satellite cells attract monocytes and use macrophages as a support to escape apoptosis and enhance muscle growth. J Cell Biol. 2003 Dec 8;163(5):1133-43. doi: 10.1083/jcb.200212046. PMID: 14662751; PMCID: PMC2173611.
[21]	ARNOLD L, HENRY A, PORON F, et al. Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis[J/OL]. The Journal of Experimental Medicine, 2007, 204(5): 1057-1069. DOI:10.1084/jem.20070075.
[22]	SORKIN M, HUBER A K, HWANG C, et al. Regulation of heterotopic ossification by monocytes in a mouse model of aberrant wound healing[J/OL]. Nature Communications, 2020, 11(1): 722. DOI:10.1038/s41467-019-14172-4.
[23]	ZHANG H, CAI D, BAI X. Macrophages regulate the progression of osteoarthritis[J/OL]. Osteoarthritis and Cartilage, 2020, 28(5): 555-561. DOI:10.1016/j.joca.2020.01.007.
[24]	AASHAQ S, BATOOL A, MIR S A, et al. TGF-β signaling: A recap of SMAD-independent and SMAD-dependent pathways[J/OL]. Journal of Cellular Physiology, 2022, 237(1): 59-85. DOI:10.1002/jcp.30529.
[25]	OLMSTED-DAVIS E, MEJIA J, SALISBURY E, et al. A Population of M2 Macrophages Associated With Bone Formation[J/OL]. Frontiers in Immunology, 2021, 12[2022-08-28]. https://www.frontiersin.org/articles/10.3389/fimmu.2021.686769.
[26]	LI J, SUN Z, LUO G, et al. Quercetin Attenuates Trauma-Induced Heterotopic Ossification by Tuning Immune Cell Infiltration and Related Inflammatory Insult[J/OL]. Frontiers in Immunology, 2021, 12: 649285. DOI:10.3389/fimmu.2021.649285.
[27]	FERNANDES T L, GOMOLL A H, LATTERMANN C, et al. Macrophage: A Potential Target on Cartilage Regeneration[J/OL]. Frontiers in Immunology, 2020, 11: 111. DOI:10.3389/fimmu.2020.00111.
[28]	SPILLER K L, ANFANG R R, SPILLER K J, et al. The role of macrophage phenotype in vascularization of tissue engineering scaffolds[J/OL]. Biomaterials, 2014, 35(15): 4477-4488. DOI:10.1016/j.biomaterials.2014.02.012.
[29]	IAVARONE F, GUARDIOLA O, SCAGLIOLA A, et al. Cripto shapes macrophage plasticity and restricts EndMT in injured and diseased skeletal muscle[J/OL]. EMBO reports, 2020, 21(4): e49075. DOI:10.15252/embr.201949075.
[30]	ZORDAN P, RIGAMONTI E, FREUDENBERG K, et al. Macrophages commit postnatal endothelium-derived progenitors to angiogenesis and restrict endothelial to mesenchymal transition during muscle regeneration[J/OL]. Cell Death & Disease, 2014, 5(1): e1031. DOI:10.1038/cddis.2013.558.
[31]	LIU Y, XU R, GU H, et al. Metabolic reprogramming in macrophage responses[J/OL]. Biomarker Research, 2021, 9(1): 1. DOI:10.1186/s40364-020-00251-y.
[32]	PéREZ S, RIUS-PéREZ S. Macrophage Polarization and Reprogramming in Acute Inflammation: A Redox Perspective[J/OL]. Antioxidants (Basel, Switzerland), 2022, 11(7): 1394. DOI:10.3390/antiox11071394.
[33]	EL KASMI K C, STENMARK K R. Contribution of metabolic reprogramming to macrophage plasticity and function[J/OL]. Seminars in Immunology, 2015, 27(4): 267-275. DOI:10.1016/j.smim.2015.09.001.
[34]	HASCHEMI A, KOSMA P, GILLE L, et al. The sedoheptulose kinase CARKL directs macrophage polarization through control of glucose metabolism[J/OL]. Cell Metabolism, 2012, 15(6): 813-826. DOI:10.1016/j.cmet.2012.04.023.
[35]	NOE J T, MITCHELL R A. Tricarboxylic acid cycle metabolites in the control of macrophage activation and effector phenotypes[J/OL]. Journal of Leukocyte Biology, 2019, 106(2): 359-367. DOI:10.1002/JLB.3RU1218-496R.
[36]	SOTO-HEREDERO G, GóMEZ DE LAS HERAS M M, GABANDé-RODRíGUEZ E, et al. Glycolysis – a key player in the inflammatory response[J/OL]. The FEBS Journal, 2020, 287(16): 3350-3369. DOI:10.1111/febs.15327.
[37]	GUO R, ZONG S, WU M, et al. Architecture of Human Mitochondrial Respiratory Megacomplex I2III2IV2[J/OL]. Cell, 2017, 170(6): 1247-1257.e12. DOI:10.1016/j.cell.2017.07.050.
[38]	DAVIS E L, SALISBURY E A, OLMSTED-DAVIS E, et al. Anaplerotic Accumulation of Tricarboxylic Acid Cycle Intermediates as Well as Changes in Other Key Metabolites During Heterotopic Ossification[J/OL]. Journal of Cellular Biochemistry, 2016, 117(4): 1044-1053. DOI:10.1002/jcb.25454.
[39]	GALVáN-PE?A S, O’NEILL L A J. Metabolic reprograming in macrophage polarization[J/OL]. Frontiers in Immunology, 2014, 5: 420. DOI:10.3389/fimmu.2014.00420.
[40]	BRUNELLE J K, BELL E L, QUESADA N M, et al. Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation[J/OL]. Cell Metabolism, 2005, 1(6): 409-414. DOI:10.1016/j.cmet.2005.05.002.
[41]	LUO W, SEMENZA G L. Emerging roles of PKM2 in cell metabolism and cancer progression[J/OL]. Trends in Endocrinology & Metabolism, 2012, 23(11): 560-566. DOI:10.1016/j.tem.2012.06.010.
[42]	LUO W, HU H, CHANG R, et al. Pyruvate Kinase M2 Is a PHD3-Stimulated Coactivator for Hypoxia-Inducible Factor 1[J/OL]. Cell, 2011, 145(5): 732-744. DOI:10.1016/j.cell.2011.03.054.
[43]	PALSSON-MCDERMOTT E M, CURTIS A M, 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 Metabolism, 2015, 21(1): 65-80. DOI:10.1016/j.cmet.2014.12.005.
[44]	YANG P, LI Z, FU R, et al. Pyruvate kinase M2 facilitates colon cancer cell migration via the modulation of STAT3 signalling[J/OL]. Cellular Signalling, 2014, 26(9): 1853-1862. DOI:10.1016/j.cellsig.2014.03.020.
[45]	DEMARIA M, GIORGI C, LEBIEDZINSKA M, et al. A STAT3-mediated metabolic switch is involved in tumour transformation and STAT3 addiction[J/OL]. Aging, 2010, 2(11): 823-842. DOI:10.18632/aging.100232.
[46]	AKRAM M. Citric acid cycle and role of its intermediates in metabolism[J/OL]. Cell Biochemistry and Biophysics, 2014, 68(3): 475-478. DOI:10.1007/s12013-013-9750-1.
[47]	EVERTS B, AMIEL E, HUANG S C C, et al. TLR-driven early glycolytic reprogramming via the kinases TBK1-IKK? supports the anabolic demands of dendritic cell activation[J/OL]. Nature Immunology, 2014, 15(4): 323-332. DOI:10.1038/ni.2833.
[48]	TANNAHILL G M, CURTIS A M, ADAMIK J, et al. Succinate is an inflammatory signal that induces IL-1β through HIF-1α[J/OL]. Nature, 2013, 496(7444): 238-242. DOI:10.1038/nature11986.
[49]	INFANTINO V, CONVERTINI P, CUCCI L, et al. The mitochondrial citrate carrier: a new player in inflammation[J/OL]. The Biochemical Journal, 2011, 438(3): 433-436. DOI:10.1042/BJ20111275.
[50]	INFANTINO V, IACOBAZZI V, MENGA A, et al. A key role of the mitochondrial citrate carrier (SLC25A1) in TNFα- and IFNγ-triggered inflammation[J/OL]. Biochimica Et Biophysica Acta, 2014, 1839(11): 1217-1225. DOI : 10.1016/j.bbagrm.2014.07.013.
[51]	PALMIERI F. The mitochondrial transporter family (SLC25): physiological and pathological implications[J/OL]. Pflugers Archiv: European Journal of Physiology, 2004, 447(5): 689-709. DOI:10.1007/s00424-003-1099-7.
[52]	PALMIERI E M, SPERA I, MENGA A, et al. Acetylation of human mitochondrial citrate carrier modulates mitochondrial citrate/malate exchange activity to sustain NADPH production during macrophage activation[J/OL]. Biochimica Et Biophysica Acta, 2015, 1847(8): 729-738. DOI:10.1016/j.bbabio.2015.04.009.
[53]	SAGGERSON D. Malonyl-CoA, a key signaling molecule in mammalian cells[J/OL]. Annual Review of Nutrition, 2008, 28: 253-272. DOI:10.1146/annurev.nutr.28.061807.155434.
[54]	CHOUDHARY C, WEINERT B T, NISHIDA Y, et al. The growing landscape of lysine acetylation links metabolism and cell signalling[J/OL]. Nature Reviews. Molecular Cell Biology, 2014, 15(8): 536-550. DOI:10.1038/nrm3841.
[55]	DASKALAKI M G, TSATSANIS C, KAMPRANIS S C. Histone methylation and acetylation in macrophages as a mechanism for regulation of inflammatory responses[J/OL]. Journal of Cellular Physiology, 2018, 233(9): 6495-6507. DOI:10.1002/jcp.26497.
[56]	CHOUCHANI E T, PELL V R, GAUDE E, et al. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS[J/OL]. Nature, 2014, 515(7527): 431-435. DOI:10.1038/nature13909.
[57]	JHA A K, HUANG S C C, SERGUSHICHEV A, et al. Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization[J/OL]. Immunity, 2015, 42(3): 419-430. DOI:10.1016/j.immuni.2015.02.005.
[58]	DR?SE S. Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning[J/OL]. Biochimica Et Biophysica Acta, 2013, 1827(5): 578-587. DOI:10.1016/j.bbabio.2013.01.004.
[59]	BROWN G C. Nitric oxide and mitochondrial respiration[J/OL]. Biochimica Et Biophysica Acta, 1999, 1411(2-3): 351-369. DOI:10.1016/s0005-2728(99)00025-0.
[60]	RUBIC T, LAMETSCHWANDTNER G, JOST S, et al. Triggering the succinate receptor GPR91 on dendritic cells enhances immunity[J/OL]. Nature Immunology, 2008, 9(11): 1261-1269. DOI:10.1038/ni.1657.

Glycolytic reprogramming of macrophages in heterotopic ossification

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