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REVIEW

Macrophage Polarization and the Regulation of Bone Immunity in Bone Homeostasis

, , , &
Pages 3563-3580 | Received 31 May 2023, Accepted 15 Aug 2023, Published online: 22 Aug 2023

References

  • Chen X, Zhi X, Yin Z, et al. 18β-glycyrrhetinic acid inhibits osteoclastogenesis in vivo and in vitro by blocking RANKL-mediated RANK–TRAF6 interactions and NF-κB and MAPK signaling pathways. Front Pharmacol. 2018;9:647. doi:10.3389/fphar.2018.00647
  • Li J, Yin Z, Huang B, Xu K, Su J. Stat3 signaling pathway: a future therapeutic target for bone-related diseases. Front Pharmacol. 2022;13:897539. doi:10.3389/fphar.2022.897539
  • Muñoz J, Akhavan NS, Mullins AP, Arjmandi BH. Macrophage polarization and osteoporosis: a review. Nutrients. 2020;12(10). doi:10.3390/nu12102999
  • Sun Y, Li J, Xie X, et al. Macrophage-osteoclast associations: origin, polarization, and subgroups. Front Immunol. 2021;12:778078. doi:10.3389/fimmu.2021.778078
  • Chen K, Jiao Y, Liu L, et al. Communications between bone marrow macrophages and bone cells in bone remodeling. Front Cell Dev Biol. 2020;8:598263. doi:10.3389/fcell.2020.598263
  • Muñoz M, Robinson K, Shibli-Rahhal A. Bone health and osteoporosis prevention and treatment. Clin Obstet Gynecol. 2020;63(4):770–787. doi:10.1097/grf.0000000000000572
  • Molendijk M, Hazes JM, Lubberts E. From patients with arthralgia, pre-RA and recently diagnosed RA: what is the current status of understanding RA pathogenesis? RMD Open. 2018;4(1):e000256. doi:10.1136/rmdopen-2016-000256
  • Wang A, Ren M, Wang J. The pathogenesis of steroid-induced osteonecrosis of the femoral head: a systematic review of the literature. Gene. 2018;671:103–109. doi:10.1016/j.gene.2018.05.091
  • Yadav S, Dwivedi A, Tripathi A. Biology of macrophage fate decision: implication in inflammatory disorders. Cell Biol Int. 2022;46(10):1539–1556.
  • Razi S, Yaghmoorian Khojini J, Kargarijam F, et al. Macrophage efferocytosis in health and disease. Cell biochemistry and Function. 2023;41(2):152–165. doi:10.1002/cbf.3780
  • Orecchioni M, Ghosheh Y, Pramod AB, Ley K. Macrophage polarization: different gene signatures in M1(LPS+) vs. classically and M2(LPS-) vs. alternatively activated macrophages. Front Immunol. 2019;10:1084.
  • Tian T, Wang Z, Chen L, Xu W, Wu B. Photobiomodulation activates undifferentiated macrophages and promotes M1/M2 macrophage polarization via PI3K/AKT/mTOR signaling pathway. Laser med sci. 2023;38(1):86. doi:10.1007/s10753-022-01777-z
  • He X, Tan S, Shao Z, Wang X. Latitudinal and longitudinal regulation of tissue macrophages in inflammatory diseases. Genes Dis. 2022;9(5):1194–1207.
  • Gharavi AT, Hanjani NA, Movahed E, Doroudian M. The role of macrophage subtypes and exosomes in immunomodulation. Cell Mol Biol Lett. 2022;27(1):83.
  • Li P, Ma C, Li J, et al. Proteomic characterization of four subtypes of M2 macrophages derived from human THP-1 cells. J Zhejiang Univ Sci B. 2022;23(5):407–422.
  • García-García A, Pigeot S, Martin I. Engineering of immunoinstructive extracellular matrices for enhanced osteoinductivity. Bioact Mater. 2023;24:174–184.
  • Zou Z, Lin H, Li M, Lin B. Tumor-associated macrophage polarization in the inflammatory tumor microenvironment. Front Oncol. 2023;13:1103149.
  • Deng L, Jian Z, Xu T, et al. Macrophage Polarization: An Important Candidate Regulator for Lung Diseases. Molecules. 2023;28(5):2379.
  • Shanley LC, Mahon OR, O’Rourke SA, et al. Macrophage metabolic profile is altered by hydroxyapatite particle size. Acta Biomater. 2023;160:311–321. doi:10.1016/j.actbio.2023.01.058
  • Sun X, Gao Y, Li Z, He J, Wu Y. Magnetic responsive hydroxyapatite scaffold modulated macrophage polarization through PPAR/JAK-STAT signaling and enhanced fatty acid metabolism. Biomaterials. 2023;295:122051. doi:10.1016/j.biomaterials.2023.122051
  • Liu J, Wang F, Luo F. The role of JAK/STAT pathway in fibrotic diseases: molecular and cellular mechanisms. Biomolecules. 2023;13(1). doi:10.3390/biom13010119
  • Owen KL, Brockwell NK, Parker BS. JAK-STAT signaling: a double-edged sword of immune regulation and cancer progression. Cancers. 2019;11(12). doi:10.3390/cancers11122002
  • Hu X, Li J, Fu M, Zhao X, Wang W. The JAK/STAT signaling pathway: from bench to clinic. Signal Transduct Target Ther. 2021;6(1):402. doi:10.1038/s41392-021-00791-1
  • Verhoeven Y, Tilborghs S, Jacobs J, et al. The potential and controversy of targeting STAT family members in cancer. Semin Cancer Biol. 2020;60:41–56. doi:10.1016/j.semcancer.2019.10.002
  • Ernst S, Müller-Newen G. Nucleocytoplasmic shuttling of STATs. A target for intervention? Cancers. 2019;11(11). doi:10.3390/cancers11111815
  • Kawakami T, Koike A, Maehara T, Hayashi T, Fujimori K. Bicarbonate enhances the inflammatory response by activating JAK/STAT signalling in LPS + IFN-γ-stimulated macrophages. J Biochem. 2020;167(6):623–631. doi:10.1093/jb/mvaa010
  • Wu L, Sun S, Qu F, et al. CXCL9 influences the tumor immune microenvironment by stimulating JAK/STAT pathway in triple-negative breast cancer. Cancer Immunol Immunother. 2022. doi:10.1007/s00262-022-03343-w
  • Li X, Jiang M, Chen X, Sun W. Etanercept alleviates psoriasis by reducing the Th17/Treg ratio and promoting M2 polarization of macrophages. Immun Inflamm Dis. 2022;10(12):e734. doi:10.1002/iid3.734
  • Wang X, Chen S, Lu R, et al. Adipose-derived stem cell-secreted exosomes enhance angiogenesis by promoting macrophage M2 polarization in type 2 diabetic mice with limb ischemia via the JAK/STAT6 pathway. Heliyon. 2022;8(11):e11495. doi:10.1016/j.heliyon.2022.e11495
  • Tu Y, Liu J, Kong D, et al. Irisin drives macrophage anti-inflammatory differentiation via JAK2-STAT6-dependent activation of PPARγ and Nrf2 signaling. Free Radic Biol Med. 2023. doi:10.1016/j.freeradbiomed.2023.03.014
  • Xu L, Zhang Y, Dai Q, et al. Scorpion venom polypeptide governs alveolar macrophage M1/M2 polarization to alleviate pulmonary fibrosis. Tissue Cell. 2022;79:101939. doi:10.1016/j.tice.2022.101939
  • Song M, Cui X, Zhang J, et al. Shenlian extract attenuates myocardial ischaemia-reperfusion injury via inhibiting M1 macrophage polarization by silencing miR-155. Pharm Biol. 2022;60(1):2011–2024. doi:10.1080/13880209.2022.2117828
  • Tajalli-Nezhad S, Mohammadi S, Atlasi MA, et al. Calcitriol modulate post-ischemic TLR signaling pathway in ischemic stroke patients. J Neuroimmunol. 2023;375:578013. doi:10.1016/j.jneuroim.2022.578013
  • Zhu W, Xu R, Du J, et al. Zoledronic acid promotes TLR-4-mediated M1 macrophage polarization in bisphosphonate-related osteonecrosis of the jaw. FASEB J. 2019;33(4):5208–5219. doi:10.1096/fj.201801791RR
  • Wang Y, Wu Y, Sailike J, et al. Fourteen composite probiotics alleviate type 2 diabetes through modulating gut microbiota and modifying M1/M2 phenotype macrophage in db/db mice. Pharmacol Res. 2020;161:105150. doi:10.1016/j.phrs.2020.105150
  • Kang Z-P, Wang M-X, T-t W, et al. Curcumin alleviated dextran sulfate sodium-induced colitis by regulating M1/M2 macrophage polarization and TLRs signaling pathway. Evid Based Complement Alternat Med. 2021;2021:3334994. doi:10.1155/2021/3334994
  • Zhou L, Zhao H, Zhao H, et al. GBP5 exacerbates rosacea-like skin inflammation by skewing macrophage polarization towards M1 phenotype through the NF-κB signalling pathway. J Eur Acad Dermatol Venereol. 2023;37(4):796–809. doi:10.1111/jdv.18725
  • Lee H, Han J-H, Ahn K, et al. Recombinant human KAI1/CD82 attenuates M1 macrophage polarization on LPS-stimulated RAW264.7 cells via blocking TLR4/JNK/NF-κB signal pathway. BMB Rep. 2023;2023:1.
  • Tian P, Zhao L, Kim J, et al. Dual stimulus responsive borosilicate glass (BSG) scaffolds promote diabetic alveolar bone defectsrepair by modulating macrophage phenotype. Bioact Mater. 2023;26:231–248. doi:10.1016/j.bioactmat.2023.02.023
  • Xie Y, Shi X, Sheng K, et al. PI3K/Akt signaling transduction pathway, erythropoiesis and glycolysis in hypoxia. Mol Med Rep. 2019;19(2):783–791. doi:10.3892/mmr.2018.9713
  • Wang J, Hu K, Cai X, et al. Targeting PI3K/AKT signaling for treatment of idiopathic pulmonary fibrosis. Acta Pharm Sin B. 2022;12(1):18–32. doi:10.1016/j.apsb.2021.07.023
  • He X, Xiao J, Li Z, et al. Inhibition of PD-1 alters the SHP1/2-PI3K/Akt axis to decrease M1 polarization of alveolar macrophages in lung ischemia-reperfusion injury. Inflammation. 2023;46(2):639–654. doi:10.1007/s10753-022-01762-6
  • Tian T, Chen L, Wang Z, Zhu M, Xu W, Wu B. Sema3A drives alternative macrophage activation in the resolution of periodontitis via PI3K/AKT/mTOR signaling. Inflammation. 2023. doi:10.1007/s10753-022-01777-z
  • Wang Y, Zhang X, Wang J, et al. Inflammatory periodontal ligament stem cells drive M1 macrophage polarization via exosomal miR-143-3p-mediated regulation of PI3K/AKT/NF-κB signaling. Stem Cells. 2023;41(2):184–199. doi:10.1093/stmcls/sxac087
  • Wang C, Zhang M, Yan J, et al. Chemokine-like receptor 1 deficiency impedes macrophage phenotypic transformation and cardiac repair after myocardial infarction. Int J Cardiol. 2023;372. doi:10.1016/j.ijcard.2022.12.015
  • Yang B, Wang L, Tian Z. Silencing of RhoC induces macrophage M1 polarization to inhibit migration and invasion in colon cancer via regulating the PTEN/FOXO1 pathway. Int J Exp Pathol. 2023;104(1):33–42. doi:10.1111/iep.12460
  • Xu J, Chen P, Yu C, et al. Hypoxic bone marrow mesenchymal stromal cells-derived exosomal miR-182-5p promotes liver regeneration via FOXO1-mediated macrophage polarization. FASEB J. 2022;36(10):e22553. doi:10.1096/fj.202101868RRR
  • Wu X, Wang Y, Chen H, Wang Y, Gu Y. Phosphatase and tensin homologue determine inflammatory status by differentially regulating the expression of Akt1 and Akt2 in macrophage alternative polarization of periodontitis. J Clin Periodontol. 2023;50(2):220–231. doi:10.1111/jcpe.13730
  • Matsuno K. Notch signaling. Dev Growth Differ. 2020;62(1):3. doi:10.1111/dgd.12642
  • Meurette O, Mehlen P. Notch signaling in the tumor microenvironment. Cancer Cell. 2018;34(4):536–548. doi:10.1016/j.ccell.2018.07.009
  • Xu H, Zhu J, Smith S, et al. Notch-RBP-J signaling regulates the transcription factor IRF8 to promote inflammatory macrophage polarization. Nat Immunol. 2012;13(7):642–650. doi:10.1038/ni.2304
  • Wu Y, Liang M, Huang F, et al. Notch blockade specifically in bone marrow-derived FSP-1-positive cells ameliorates renal fibrosis. Cells. 2023;12(2). doi:10.3390/cells12020214
  • Chen X, Su C, Wei Q, Sun H, Xie J, Nong G. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate diffuse alveolar hemorrhage associated with systemic lupus erythematosus in mice by promoting M2 macrophage polarization via the microRNA-146a-5p/NOTCH1 axis. Immunol Invest. 2022;51(7):1975–1993. doi:10.1080/08820139.2022.2090261
  • Yang Y, Ni M, Zong R, et al. Targeting notch1-YAP circuit reprograms macrophage polarization and alleviates acute liver injury in mice. Cell Mol Gastroenterol Hepatol. 2023;15(5):1085–1104. doi:10.1016/j.jcmgh.2023.01.002
  • Ikeda H, Kakeya H. Targeting hypoxia-inducible factor 1 (HIF-1) signaling with natural products toward cancer chemotherapy. J Antibiot (Tokyo). 2021;74(10):687–695. doi:10.1038/s41429-021-00451-0
  • Suresh MV, Balijepalli S, Solanki S, et al. Hypoxia-inducible factor 1α and its role in lung injury: adaptive or maladaptive. Inflammation. 2023;46(2):491–508. doi:10.1007/s10753-022-01769-z
  • Díaz-Bulnes P, Saiz ML, López-Larrea C, Rodríguez RM. Crosstalk between hypoxia and ER stress response: a key regulator of macrophage polarization. Front Immunol. 2019;10:2951. doi:10.3389/fimmu.2019.02951
  • Chen L, Yang J, Zhang M, Fu D, Luo H, Yang X. SPP1 exacerbates ARDS via elevating Th17/Treg and M1/M2 ratios through suppression of ubiquitination-dependent HIF-1α degradation. Cytokine. 2023;164:156107. doi:10.1016/j.cyto.2022.156107
  • Li Y, Liang Q, Zhou L, et al. An ROS-responsive artesunate prodrug nanosystem co-delivers dexamethasone for rheumatoid arthritis treatment through the HIF-1α/NF-κB cascade regulation of ROS scavenging and macrophage repolarization. Acta Biomater. 2022;152:406–424. doi:10.1016/j.actbio.2022.08.054
  • Ponzetti M, Rucci N. Osteoblast differentiation and signaling: established concepts and emerging topics. Int J Mol Sci. 2021;22(13). doi:10.3390/ijms22136651
  • Schlundt C, Fischer H, Bucher CH, Rendenbach C, Duda GN, Schmidt-Bleek K. The multifaceted roles of macrophages in bone regeneration: a story of polarization, activation and time. Acta Biomater. 2021;133:46–57. doi:10.1016/j.actbio.2021.04.052
  • Batoon L, Millard SM, Wullschleger ME, et al. CD169+ macrophages are critical for osteoblast maintenance and promote intramembranous and endochondral ossification during bone repair. Biomaterials. 2019;196:51–66. doi:10.1016/j.biomaterials.2017.10.033
  • You Y, Wang W, Li Y, et al. Aspirin/PLGA coated 3D-printed Ti-6Al-4V alloy modulate macrophage polarization to enhance osteoblast differentiation and osseointegration. J Mater Sci Mater Med. 2022;33(10):73. doi:10.1007/s10856-022-06697-w
  • Shi C, Yuan F, Li Z, et al. MSN@IL-4 sustainingly mediates macrophagocyte M2 polarization and relieves osteoblast damage via NF-κB pathway-associated apoptosis. Biomed Res Int. 2022;2022:2898729. doi:10.1155/2022/2898729
  • Osta B, Benedetti G, Miossec P. Classical and paradoxical effects of TNF-α on bone homeostasis. Front Immunol. 2014;5:48. doi:10.3389/fimmu.2014.00048
  • Zhao M, Dai W, Wang H, et al. Periodontal ligament fibroblasts regulate osteoblasts by exosome secretion induced by inflammatory stimuli. Arch Oral Biol. 2019;105:27–34. doi:10.1016/j.archoralbio.2019.06.002
  • Glass GE, Chan JK, Freidin A, Feldmann M, Horwood NJ, Nanchahal J. TNF-alpha promotes fracture repair by augmenting the recruitment and differentiation of muscle-derived stromal cells. Proc Natl Acad Sci USA. 2011;108(4):1585–1590. doi:10.1073/pnas.1018501108
  • Kaneshiro S, Ebina K, Shi K, et al. IL-6 negatively regulates osteoblast differentiation through the SHP2/MEK2 and SHP2/Akt2 pathways in vitro. J Bone Miner Metab. 2014;32(4):378–392.
  • Yeh L-C-C, Zavala MC, Lee JC. Osteogenic protein-1 and interleukin-6 with its soluble receptor synergistically stimulate rat osteoblastic cell differentiation. J Cell Physiol. 2002;190(3):322–331.
  • Chen S, Ni S, Liu C, et al. Neglected immunoregulation: M2 polarization of macrophages triggered by low-dose irradiation plays an important role in bone regeneration. J Cell Mol Med. 2023. doi:10.1111/jcmm.17721
  • Wu M, Chen G, Li Y-P. TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease. Bone Res. 2016;4:16009. doi:10.1038/boneres.2016.9
  • Shen H, Kushioka J, Toya M, et al. Sex differences in the therapeutic effect of unaltered versus NFκB sensing IL-4 over-expressing mesenchymal stromal cells in a murine model of chronic inflammatory bone loss. Front Bioeng Biotechnol. 2022;10:962114. doi:10.3389/fbioe.2022.962114
  • Zhang B, Yang Y, Yi J, Zhao Z, Ye R. Hyperglycemia modulates M1/M2 macrophage polarization via reactive oxygen species overproduction in ligature-induced periodontitis. J Periodontal Res. 2021;56(5):1.
  • Zha L, He L, Liang Y, et al. TNF-α contributes to postmenopausal osteoporosis by synergistically promoting RANKL-induced osteoclast formation. Biomed Pharmacother. 2018;102:369–374. doi:10.1016/j.biopha.2018.03.080
  • Marahleh A, Kitaura H, Ohori F, et al. TNF-α directly enhances osteocyte RANKL expression and promotes osteoclast formation. Front Immunol. 2019;10:2925. doi:10.3389/fimmu.2019.02925
  • AlQranei MS, Senbanjo LT, Aljohani H, Hamza T, Chellaiah MA. Lipopolysaccharide- TLR-4 axis regulates osteoclastogenesis independent of RANKL/RANK signaling. BMC Immunol. 2021;22(1):23. doi:10.1186/s12865-021-00409-9
  • Ye Q, Xu H, Liu S, et al. Apoptotic extracellular vesicles alleviate Pg-LPS induced inflammatory responses of macrophages via AMPK/SIRT1/NF-κB pathway and inhibit osteoclast formation. J Periodontol. 2022;93(11):1738–1751. doi:10.1002/JPER.21-0657
  • Xing L, Carlson L, Story B, et al. Expression of either NF-kappaB p50 or p52 in osteoclast precursors is required for IL-1-induced bone resorption. J Bone Miner Res. 2003;18(2):260–269.
  • Kurihara N, Bertolini D, Suda T, Akiyama Y, Roodman GD. IL-6 stimulates osteoclast-like multinucleated cell formation in long term human marrow cultures by inducing IL-1 release. J Immunol. 1990;144(11):4226–4230.
  • Otsuka Y, Kondo T, Aoki H, et al. IL-1β promotes osteoclastogenesis by increasing the expression of IGF2 and chemokines in non-osteoclastic cells. J Pharmacol Sci. 2023;151(1):1–8. doi:10.1016/j.jphs.2022.10.007
  • Levescot A, Chang MH, Schnell J, et al. IL-1β-driven osteoclastogenic Tregs accelerate bone erosion in arthritis. J Clin Invest. 2021;131(18):1.
  • Deng Z, Zhang R, Li M, et al. STAT3/IL-6 dependent induction of inflammatory response in osteoblast and osteoclast formation in nanoscale wear particle-induced aseptic prosthesis loosening. Biomater Sci. 2021;9(4):1291–1300. doi:10.1039/d0bm01256d
  • Feng W, Liu H, Luo T, et al. Combination of IL-6 and sIL-6R differentially regulate varying levels of RANKL-induced osteoclastogenesis through NF-κB, ERK and JNK signaling pathways. Sci Rep. 2017;7:41411. doi:10.1038/srep41411
  • Liu -Q-Q, W-w W, Yang J, et al. A GP130-targeting small molecule, LMT-28, reduces LPS-induced bone resorption around implants in diabetic models by inhibiting IL-6/GP130/JAK2/STAT3 signaling. Mediators Inflamm. 2023;2023:9330439. doi:10.1155/2023/9330439
  • Fujii T, Kitaura H, Kimura K, Hakami ZW, Takano-Yamamoto T. IL-4 inhibits TNF-α-mediated osteoclast formation by inhibition of RANKL expression in TNF-α-activated stromal cells and direct inhibition of TNF-α-activated osteoclast precursors via a T-cell-independent mechanism in vivo. Bone. 2012;51(4):771–780. doi:10.1016/j.bone.2012.06.024
  • Palmqvist P, Lundberg P, Persson E, et al. Inhibition of hormone and cytokine-stimulated osteoclastogenesis and bone resorption by interleukin-4 and interleukin-13 is associated with increased osteoprotegerin and decreased RANKL and RANK in a STAT6-dependent pathway. J Biol Chem. 2006;281(5):2414–2429.
  • Bendixen AC, Shevde NK, Dienger KM, Willson TM, Funk CD, Pike JW. IL-4 inhibits osteoclast formation through a direct action on osteoclast precursors via peroxisome proliferator-activated receptor gamma 1. Proc Natl Acad Sci USA. 2001;98(5):2443–2448.
  • Moreno JL, Kaczmarek M, Keegan AD, Tondravi M. IL-4 suppresses osteoclast development and mature osteoclast function by a STAT6-dependent mechanism: irreversible inhibition of the differentiation program activated by RANKL. Blood. 2003;102(3):1078–1086.
  • Li S, Zhang L, Liu C, et al. Spontaneous immunomodulation and regulation of angiogenesis and osteogenesis by Sr/Cu-borosilicate glass (BSG) bone cement to repair critical bone defects. Bioact Mater. 2023;23:101–117. doi:10.1016/j.bioactmat.2022.10.021
  • Cai G, Lu Y, Zhong W, et al. Piezo1-mediated M2 macrophage mechanotransduction enhances bone formation through secretion and activation of transforming growth factor-β1. Cell Prolif. 2023:e13440. doi:10.1111/cpr.13440
  • Romero-López M, Li Z, Rhee C, et al. Macrophage effects on mesenchymal stem cell osteogenesis in a three-dimensional in vitro bone model. Tissue Eng Part A. 2020;26(19–20):1099–1111. doi:10.1089/ten.TEA.2020.0041
  • Qi Y, Zhu T, Zhang T, et al. M1 macrophage-derived exosomes transfer miR-222 to induce bone marrow mesenchymal stem cell apoptosis. Lab Invest. 2021;101(10):1318–1326. doi:10.1038/s41374-021-00622-5
  • Wang F, Kong L, Wang W, et al. Adrenomedullin 2 improves bone regeneration in type 1 diabetic rats by restoring imbalanced macrophage polarization and impaired osteogenesis. Stem Cell Res Ther. 2021;12(1):288. doi:10.1186/s13287-021-02368-9
  • Yang L, Xiao L, Gao W, et al. Macrophages at low-inflammatory status improved osteogenesis via autophagy regulation. Tissue Eng Part A. 2021. doi:10.1089/ten.TEA.2021.0015
  • Chen X, Wan Z, Yang L, et al. Exosomes derived from reparative M2-like macrophages prevent bone loss in murine periodontitis models via IL-10 mRNA. J Nanobiotechnology. 2022;20(1):110. doi:10.1186/s12951-022-01314-y
  • Lu Y, Liu S, Yang P, et al. Exendin-4 and eldecalcitol synergistically promote osteogenic differentiation of bone marrow mesenchymal stem cells through M2 macrophages polarization via PI3K/AKT pathway. Stem Cell Res Ther. 2022;13(1):113. doi:10.1186/s13287-022-02800-8
  • Zhang J, Shi H, Zhang N, Hu L, Jing W, Pan J. Interleukin-4-loaded hydrogel scaffold regulates macrophages polarization to promote bone mesenchymal stem cells osteogenic differentiation via TGF-β1/Smad pathway for repair of bone defect. Cell Prolif. 2020;53(10):e12907. doi:10.1111/cpr.12907
  • Yu K, Huangfu H, Qin Q, et al. Application of bone marrow-derived macrophages combined with bone mesenchymal stem cells in dual-channel three-dimensional bioprinting scaffolds for early immune regulation and osteogenic induction in rat calvarial defects. ACS Appl Mater Interfaces. 2022;14(41):47052–47065. doi:10.1021/acsami.2c13557
  • Jiang Q, Bai G, Liu X, et al. 3D GelMA ICC scaffolds combined with SW033291 for bone regeneration by modulating macrophage polarization. Pharmaceutics. 2021;13(11). doi:10.3390/pharmaceutics13111934
  • Yong EL, Logan S. Menopausal osteoporosis: screening, prevention and treatment. Singapore Med J. 2021;62(4):159–166. doi:10.11622/smedj.2021036
  • Zhang W, Gao R, Rong X, et al. Immunoporosis: role of immune system in the pathophysiology of different types of osteoporosis. Front Endocrinol. 2022;13:965258. doi:10.3389/fendo.2022.965258
  • Dou C, Ding N, Zhao C, et al. Estrogen deficiency-mediated M2 macrophage osteoclastogenesis contributes to M1/M2 ratio alteration in ovariectomized osteoporotic mice. J Bone Miner Res. 2018;33(5):899–908. doi:10.1002/jbmr.3364
  • Brunetti G, Storlino G, Oranger A, et al. LIGHT/TNFSF14 regulates estrogen deficiency-induced bone loss. J Pathol. 2020;250(4):440–451. doi:10.1002/path.5385
  • Yu L, Hu M, Cui X, et al. M1 macrophage-derived exosomes aggravate bone loss in postmenopausal osteoporosis via a microRNA-98/DUSP1/JNK axis. Cell Biol Int. 2021;45(12):2452–2463. doi:10.1002/cbin.11690
  • Batoon L, Millard SM, Raggatt LJ, et al. Osteal macrophages support osteoclast-mediated resorption and contribute to bone pathology in a postmenopausal osteoporosis mouse model. J Bone Miner Res. 2021;36(11):2214–2228. doi:10.1002/jbmr.4413
  • Shi F, Ni L, Gao Y-M. Tetrandrine attenuates cartilage degeneration, osteoclast proliferation, and macrophage transformation through inhibiting P65 phosphorylation in ovariectomy-induced osteoporosis. Immunol Invest. 2022;51(3):465–479. doi:10.1080/08820139.2020.1837864
  • Zhang C, Zhong Z, Sang W, et al. The dibenzyl isoquinoline alkaloid berbamine ameliorates osteoporosis by inhibiting bone resorption. Front Endocrinol. 2022;13:885507. doi:10.3389/fendo.2022.885507
  • Yang Y, Sheng D, Shi J, et al. Avicularin alleviates osteoporosis-induced implant loosening by attenuating macrophage M1 polarization via its inhibitory effect on the activation of NF-κB. Biomed Pharmacother. 2023;158:114113. doi:10.1016/j.biopha.2022.114113
  • Kamal D, Trăistaru R, Kamal CK, Alexandru DO, Ion DA, Grecu DC. Macrophage response in patients diagnosed with aseptic necrosis of the femoral head presenting different risk factors. Rom J Morphol Embryol. 2015;56(1):163–168.
  • Vicaş RM, Bodog FD, Fugaru FO, et al. Histopathological and immunohistochemical aspects of bone tissue in aseptic necrosis of the femoral head. Rom J Morphol Embryol. 2020;61(4):1249–1258. doi:10.47162/RJME.61.4.26
  • Adapala NS, Yamaguchi R, Phipps M, Aruwajoye O, Kim HKW. Necrotic bone stimulates proinflammatory responses in macrophages through the activation of toll-like receptor 4. Am J Pathol. 2016;186(11):2987–2999. doi:10.1016/j.ajpath.2016.06.024
  • Jeong H, Yoon H, Lee Y, et al. SOCS3 attenuates dexamethasone-induced M2 polarization by down-regulation of GILZ via ROS- and p38 MAPK-dependent pathways. Immune Netw. 2022;22(4):e33. doi:10.4110/in.2022.22.e33
  • Busillo JM, Azzam KM, Cidlowski JA. Glucocorticoids sensitize the innate immune system through regulation of the NLRP3 inflammasome. J Biol Chem. 2011;286(44):38703–38713. doi:10.1074/jbc.M111.275370
  • Lannan EA, Galliher-Beckley AJ, Scoltock AB, Cidlowski JA. Proinflammatory actions of glucocorticoids: glucocorticoids and TNFα coregulate gene expression in vitro and in vivo. Endocrinology. 2012;153(8):3701–3712. doi:10.1210/en.2012-1020
  • Fang B, Wang D, Zheng J, et al. Involvement of tumor necrosis factor alpha in steroid-associated osteonecrosis of the femoral head: friend or foe? Stem Cell Res Ther. 2019;10(1):5. doi:10.1186/s13287-018-1112-x
  • Jin S, Meng C, He Y, et al. Curcumin prevents osteocyte apoptosis by inhibiting M1-type macrophage polarization in mice model of glucocorticoid-associated osteonecrosis of the femoral head. J Orthop Res. 2020;38(9):2020–2030. doi:10.1002/jor.24619
  • Jiang C, Zhou Z, Lin Y, et al. Astragaloside IV ameliorates steroid-induced osteonecrosis of the femoral head by repolarizing the phenotype of pro-inflammatory macrophages. Int Immunopharmacol. 2021;93:107345. doi:10.1016/j.intimp.2020.107345
  • Otón T, Carmona L. The epidemiology of established rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2019;33(5):101477. doi:10.1016/j.berh.2019.101477
  • Wang Q, Zhou X, Zhao Y, et al. Polyphyllin I ameliorates collagen-induced arthritis by suppressing the inflammation response in macrophages through the NF-κB pathway. Front Immunol. 2018;9:2091. doi:10.3389/fimmu.2018.02091
  • Van Raemdonck K, Umar S, Palasiewicz K, et al. CCL21/CCR7 signaling in macrophages promotes joint inflammation and Th17-mediated osteoclast formation in rheumatoid arthritis. Cell Mol Life Sci. 2020;77(7):1387–1399. doi:10.1007/s00018-019-03235-w
  • Hu L, Liu R, Zhang L. Advance in bone destruction participated by JAK/STAT in rheumatoid arthritis and therapeutic effect of JAK/STAT inhibitors. Int Immunopharmacol. 2022;111:109095. doi:10.1016/j.intimp.2022.109095
  • Deng C, Zhang Q, He P, et al. Targeted apoptosis of macrophages and osteoclasts in arthritic joints is effective against advanced inflammatory arthritis. Nat Commun. 2021;12(1):2174. doi:10.1038/s41467-021-22454-z
  • Ge G, Bai J, Wang Q, et al. Punicalagin ameliorates collagen-induced arthritis by downregulating M1 macrophage and pyroptosis via NF-κB signaling pathway. Sci China Life Sci. 2022;65(3):588–603. doi:10.1007/s11427-020-1939-1
  • Mahon OR, Browe DC, Gonzalez-Fernandez T, et al. Nano-particle mediated M2 macrophage polarization enhances bone formation and MSC osteogenesis in an IL-10 dependent manner. Biomaterials. 2020;239:119833. doi:10.1016/j.biomaterials.2020.119833
  • Li L, Li Q, Gui L, et al. Sequential gastrodin release PU/n-HA composite scaffolds reprogram macrophages for improved osteogenesis and angiogenesis. Bioact Mater. 2023;19:24–37. doi:10.1016/j.bioactmat.2022.03.037
  • Huang X, Chen M, Wu H, Jiao Y, Zhou C. Macrophage polarization mediated by chitooligosaccharide (COS) and associated osteogenic and angiogenic activities. ACS Biomater Sci Eng. 2020;6(3):1614–1629. doi:10.1021/acsbiomaterials.9b01550
  • Liu L, Guo S, Shi W, et al. Bone marrow mesenchymal stem cell-derived small extracellular vesicles promote periodontal regeneration. Tissue Eng Part A. 2021;27(13–14):962–976. doi:10.1089/ten.TEA.2020.0141
  • Zhu K, Yang C, Dai H, et al. Crocin inhibits titanium particle-induced inflammation and promotes osteogenesis by regulating macrophage polarization. Int Immunopharmacol. 2019;76:105865. doi:10.1016/j.intimp.2019.105865