Int J Stomatol ›› 2020, Vol. 47 ›› Issue (4): 478-483.doi: 10.7518/gjkq.2020071

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Research progress on macrophage polarization involved in the regulation of orthodontic tooth movement

Zhao Yujie1,Guan Xiaoyan1,2,Li Xiaolan3,Chen Qijun1,2,Wang Qian3,Liu Jianguo1,3()   

  1. 1. School of Stomatology, Zunyi Medical University, Zunyi 563006, China
    2. Dept. of Orthodontics, Hospital of Stomatology, Zunyi Medical University, Zunyi 563099, China
    3. The Special Key Laboratory of Oral Diseases Research, Institution of Higher Education in Guizhou Province, Zunyi 563006, China
  • Received:2019-10-14 Revised:2020-02-13 Online:2020-07-01 Published:2020-07-10
  • Contact: Jianguo Liu
  • Supported by:
    This study was supported by Program for the Key Discipline Construction Project of Guizhou Province. Guizhou Degree Word ZDXK [2017] No. 5;Provincial and Municipal Science and Technology Cooperation Special Fund Project. Province and City Branch [2014] No. 41;Expert Workstation Construction Project of Zunyi Science and Technology Bureau. Zunyi City Branch [2016] No. 18


Teeth move under orthodontic force. The plasticity of jawbone, compressive resistance of cementum, and stability of periodontal membrane environment are the biological bases of orthodontic periodontal tissue reconstruction and tooth movement. Orthodontic force on teeth affects the local periodontal microenvironment, which promotes macrophage polarization. In M1-type macrophages, the orthodontic tooth movement (OTM) secretion of inflammatory factors is conducive to alveolar bone absorption and subsequent OTM. M2-type macrophages play an anti-inflammatory role and promote the repair of periodontal tissues. This article reviews the role of M1-type and M2-type macrophages in OTM and the factors that influence macrophage polarization in orthodontic treatment. This article aims to provide theoretical basis for future research on macrophages in the orthodontic field and to accelerate OTM.

Key words: macrophage polarization, orthodontic tooth movement, root resorption, orthodontic treatment

CLC Number: 

  • R783.5


Fig 1

The biological mechanism of macrophages involved in OTM"

[1] Yang GX, Chen XY, Yan Z, et al. CD11b promotes the differentiation of osteoclasts induced by RANKL through the spleen tyrosine kinase signalling pathway[J]. J Cell Mol Med, 2017,21(12):3445-3452.
doi: 10.1111/jcmm.13254 pmid: 28661042
[2] Wang YH, Smith W, Hao DJ, et al. M1 and M2 macrophage polarization and potentially therapeutic naturally occurring compounds[J]. Int Immunophar-macol, 2019,70:459-466.
[3] Wasnik S, Rundle CH, Baylink DJ, et al. 1,25-Dihy-droxyvitamin D suppresses M1 macrophages and promotes M2 differentiation at bone injury sites[J]. JCI Insight, 2018,3(17):98773.
doi: 10.1172/jci.insight.98773 pmid: 30185660
[4] Huang CB, Alimova Y, Ebersole JL. Macrophage polarization in response to oral commensals and pathogens[J]. Pathog Dis, 2016,74(3): ftw011.
doi: 10.1093/femspd/ftw011 pmid: 26884502
[5] Juban G, Chazaud B. Metabolic regulation of macro-phages during tissue repair: insights from skeletal muscle regeneration[J]. FEBS Lett, 2017,591(19):3007-3021.
doi: 10.1002/1873-3468.12703 pmid: 28555751
[6] 阮静瑶, 陈必成, 张喜乐, 等. 巨噬细胞M1/M2极化的信号通路研究进展[J]. 免疫学杂志, 2015,31(10):911-917.
Ruan JY, Chen BC, Zhang XL, et al. Progress in signaling pathways of macrophage M1/2 polariza-tion[J]. Immunol J, 2015,31(10):911-917.
[7] Lurier EB, Dalton D, Dampier W, et al. Transcrip-tome analysis of IL-10-stimulated (M2c) macrophages by next-generation sequencing[J]. Immunobiology, 2017,222(7):847-856.
doi: 10.1016/j.imbio.2017.02.006 pmid: 28318799
[8] Annamalai RT, Turner PA, Carson WF 4th, et al. Harnessing macrophage-mediated degradation of gelatin microspheres for spatiotemporal control of BMP2 release[J]. Biomaterials, 2018,161:216-227.
doi: 10.1016/j.biomaterials.2018.01.040 pmid: 29421557
[9] Nuñez SY, Ziblat A, Secchiari F, et al. Human M2 macrophages limit NK cell effector functions through secretion of TGF-β and engagement of CD85j[J]. J Immunol, 2018,200(3):1008-1015.
doi: 10.4049/jimmunol.1700737 pmid: 29282306
[10] Hu YL, Zhang HW, Lu Y, et al. Class A scavenger receptor attenuates myocardial infarction-induced cardiomyocyte necrosis through suppressing M1 macrophage subset polarization[J]. Basic Res Car-diol, 2011,106(6):1311-1328.
[11] Li Y, Zheng W, Liu JS, et al. Expression of osteo-clastogenesis inducers in a tissue model of perio-dontal ligament under compression[J]. J Dent Res, 2011,90(1):115-120.
doi: 10.1177/0022034510385237 pmid: 20940359
[12] Tosi MF. Innate immune responses to infection[J]. J Allergy Clin Immunol, 2005,116(2):241-249.
[13] Koyama Y, Mitsui N, Suzuki N, et al. Effect of com-pressive force on the expression of inflammatory cytokines and their receptors in osteoblastic Saos-2 cells[J]. Arch Oral Biol, 2008,53(5):488-496.
pmid: 18241837
[14] Zhong JX, Chen JN, Weinkamer R, et al. In vivo effects of different orthodontic loading on root re-sorption and correlation with mechanobiological stimulus in periodontal ligament[J]. J R Soc Inter-face, 2019,16(154):20190108.
[15] Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets[J]. Nat Rev Immunol, 2011,11(11):723-737.
pmid: 21997792
[16] He D, Kou X, Yang R, et al. M1-like macrophage polarization promotes orthodontic tooth movement[J]. J Dent Res, 2015,94(9):1286-1294.
doi: 10.1177/0022034515589714 pmid: 26124217
[17] Konermann A, Beyer M, Deschner J, et al. Human periodontal ligament cells facilitate leukocyte recruit-ment and are influenced in their immunomodulatory function by Th17 cytokine release[J]. Cell Immunol, 2012,272(2):137-143.
doi: 10.1016/j.cellimm.2011.10.020 pmid: 22119482
[18] Wang Y, Zhang HW, Sun W, et al. Macrophages mediate corticotomy-accelerated orthodontic tooth movement[J]. Sci Rep, 2018,8(1):16788.
pmid: 30429494
[19] Frith JC, Mönkkönen J, Auriola S, et al. The molecular mechanism of action of the antiresorptive and antiin-flammatory drug clodronate: evidence for the forma-tion in vivo of a metabolite that inhibits bone resorp-tion and causes osteoclast and macrophage apoptosis[J]. Arthritis Rheum, 2001,44(9):2201-2210.
doi: 10.1002/1529-0131(200109)44:9<2201::aid-art374>;2-e pmid: 11592386
[20] Feller L, Khammissa RA, Thomadakis G, et al. Apical external root resorption and repair in orthodontic tooth movement: biological events[J]. Biomed Res Int, 2016,2016:4864195.
[21] Kamat M, Puranik R, Vanaki S, et al. An insight into the regulatory mechanisms of cells involved in resor-ption of dental hard tissues[J]. J Oral Maxillofac Pathol, 2013,17(2):228-233.
doi: 10.4103/0973-029X.119736 pmid: 24250084
[22] Iglesias-Linares A, Hartsfield JK Jr. Cellular and molecular pathways leading to external root resor-ption[J]. J Dent Res, 2017,96(2):145-152.
pmid: 27811065
[23] He D, Kou X, Luo Q, et al. Enhanced M1/M2 ma-crophage ratio promotes orthodontic root resorption[J]. J Dent Res, 2015,94(1):129-139.
doi: 10.1177/0022034514553817 pmid: 25344334
[24] Makrygiannakis MA, Kaklamanos EG, Athanasiou AE. Effects of systemic medication on root resor-ption associated with orthodontic tooth movement: a systematic review of animal studies[J]. Eur J Orthod, 2019,41(4):346-359.
doi: 10.1093/ejo/cjy048 pmid: 29992228
[25] Abdelmagid SM, Barbe MF, Safadi FF. Role of in-flammation in the aging bones[J]. Life Sci, 2015,123:25-34.
doi: 10.1016/j.lfs.2014.11.011 pmid: 25510309
[26] Konermann A, Stabenow D, Knolle PA, et al. Re-gulatory role of periodontal ligament fibroblasts for innate immune cell function and differentiatio[J]. Innate Immun, 2012,18(5):745-752.
pmid: 22436844
[27] Wolf M, Lossdörfer S, Craveiro R, et al. High-mobi-lity group box protein-1 released by human-perio-dontal ligament cells modulates macrophage migra-tion and activity in vitro[J]. Innate Immun, 2014,20(7):688-696.
pmid: 24107514
[28] Meikle MC. The tissue, cellular, and molecular re-gulation of orthodontic tooth movement: 100 years after Carl Sandstedt[J]. Eur J Orthod, 2006,28(3):221-240.
doi: 10.1093/ejo/cjl001 pmid: 16687469
[29] Gentek R, Molawi K, Sieweke MH. Tissue macro-phage identity and self-renewal[J]. Immunol Rev, 2014,262(1):56-73.
doi: 10.1111/imr.12224 pmid: 25319327
[30] Zeng M, Kou X, Yang R, et al. Orthodontic force induces systemic inflammatory monocyte responses[J]. J Dent Res, 2015,94(9):1295-1302.
doi: 10.1177/0022034515592868 pmid: 26130260
[31] Yamaguchi T, Movila A, Kataoka S, et al. Proinfla-mmatory M1 macrophages inhibit RANKL-induced osteoclastogenesis[J]. Infect Immun, 2016,84(10):2802-2812.
doi: 10.1128/IAI.00461-16 pmid: 27456834
[32] Pajarinen J, Lin T, Gibon E, et al. Mesenchymal stem cell-macrophage crosstalk and bone healing[J]. Biomaterials, 2019,196:80-89.
doi: 10.1016/j.biomaterials.2017.12.025 pmid: 29329642
[33] Schlundt C, El Khassawna T, Serra A, et al. Macro-phages in bone fracture healing: their essential role in endochondral ossification[J]. Bone, 2018,106:78-89.
doi: 10.1016/j.bone.2015.10.019 pmid: 26529389
[34] Zhang R, Liang Y, Wei SX. M2 macrophages are closely associated with accelerated clavicle fracture healing in patients with traumatic brain injury: a retrospective cohort study[J]. J Orthop Surg Res, 2018,13(1):213.
doi: 10.1186/s13018-018-0926-7 pmid: 30157885
[35] Sinder BP, Pettit AR, McCauley LK. Macrophages: their emerging roles in bone[J]. J Bone Miner Res, 2015,30(12):2140-2149.
doi: 10.1002/jbmr.2735 pmid: 26531055
[36] Sandberg OH, Tätting L, Bernhardsson ME, et al. Temporal role of macrophages in cancellous bone healing[J]. Bone, 2017,101:129-133.
doi: 10.1016/j.bone.2017.04.004 pmid: 28414141
[37] Loi F, Córdova LA, Zhang R, et al. The effects of immunomodulation by macrophage subsets on osteo-genesis in vitro[J]. Stem Cell Res Ther, 2016,7:15.
pmid: 26801095
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