Int J Stomatol

Int J Stomatol ›› 2025, Vol. 52 ›› Issue (4): 514-525.doi: 10.7518/gjkq.2025058

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Balance between T-helper 17 cells and regulatory T cells in bone remodeling and their impact on oral and maxillofacial damage recovery

Shuyu Zhu1(),Jing Zhou2,Zhigang Xie1()   

  1. 1.Dept. of Oral Implantology, the Affiliated Stomatology Hospital of Kunming Medical University, Kunming 650106, China
    2.Dept. of Stomatology, Yan’an Hospital, Kunming Medical University, Kunming 650051, China
  • Received:2024-09-10 Revised:2025-02-11 Online:2025-07-01 Published:2025-06-20
  • Contact: Zhigang Xie E-mail:2394105393@qq.com;13708425039@163.com
  • Supported by:
    Xingdian Talents-Medical and Health Care Talent Project(XDYC-YLWS-2023-049);Key Joint Special Project of Yunnan Provincial Science and Technology Department and Kunming Medical University(202101AY070001-025);Key Project of Yunnan Clinical Research Center for Oral Diseases(2022ZD005)

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Abstract:

Bone tissue remodeling during bone injury recovery is a well-regulated dynamic process, of which the pro-minent role of immune balance on bone homeostasis is increasingly understood. Among the various immune cells, T-hel-per 17 cells (Th17) and regulatory T cells (Treg) have attracted considerable attention because of their contradictive roles in inflammatory response and bone homeostasis. The imbalance of the Th17/Treg cell balance is closely associated with va-rious bone metabolism disorders, and regulating this balance may provide novel strategies for bone injury repair. Thus, this review focuses on the balance between Th17 and Treg in bone remodeling and their impacts on oral and maxillofacial damage recovery.

Key words: T-helper 17 cell, regulatory T cell, cell balance, osteoimmunology, periodontitis, peri-implantitis

CLC Number: 

  • R782.2

TrendMD: 

Tab 1

The function of Th17 in osteoimmunology and relevant mechanisms"

细胞功能细胞因子目标机制参考文献
Th17↑骨吸收↑IL-17↑破骨细胞调节破骨细胞的能量代谢[60]
涉及 IL-17/RANKL/TRAF6信号通路[58]
增加RANKL/OPG比例以上调破骨细胞数量及大小[57]
上调RANK并增加破骨细胞前体细胞对RANKL刺激的敏感性[56]
↓成骨细胞涉及IL-23-IL-17信号轴[47]
减少分泌ALP、OCN、Osx[68]
↑TNF-α↑破骨细胞通过RANKL促进破骨[70]
↑巨噬细胞通过NF-κB和SAPK/JNK信号通路增加巨噬细胞RANKL的表达[71]
↑B细胞诱导B细胞产生RANKL刺激破骨细胞生成，进而引发骨丢失[72]
↓成骨细胞增强Wnt信号通路抑制剂DKK1的表达[73-74]
通过增加P2Y2受体表达促进成骨细胞凋亡[75]
Th17↑ 骨生成↑IL-17↑成骨细胞、间充质干细胞促进间充质干细胞由成脂向转化为成软骨向分化[61-63]
促成骨作用可被ROS清除剂或Act1的敲除所抑制[57]
通过p-STAT3与NRF2相互作用抑制成骨细胞铁死亡[67]
促进矿化结节的形成，并增加Runx2的表达[66]

Tab 2

The function of Treg in osteoimmunology and relevant mechanisms"

细胞功能细胞因子/直接接触目标机制参考文献
Treg↓骨吸收↑IL-10↓破骨细胞上调OPG并下调RANKL和M-CSF以抑制破骨细胞的分化和成熟[78]
↓巨噬细胞抑制巨噬细胞向破骨细胞的分化[77]
↑TGF-β1↓破骨细胞通过Smad、MAPK和Bcl2途径诱导破骨细胞凋亡[81]
CTLA4↓破骨细胞前体细胞与CD80/CD86结合以促进破骨细胞前体细胞凋亡[41,80]
Treg↑ 骨生成↑TGF-β1↑成骨细胞、间充质干细胞涉及PI3K/AKT/mTOR/S6激酶1信号通路[93]
激活细胞内效应物，如MAPK和Smad相关蛋白[90,92]
Tregs促进NFAT1-SMAD3复合物在CD8+T细胞中合成，进一步驱动Wnt10b的表达[95]
发挥软骨诱导作用，抑制软骨吸收[96]
Treg↑ 骨吸收↑TGF-β1↑破骨细胞阻断Smad3与TRAF6-TAB1-TAK1复合物的结合[83]
1 Hajishengallis G, Chavakis T. Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities[J]. Nat Rev Immunol, 2021, 21(7): 426-440.
2 Jerjes W, Upile T, Petrie A, et al. Clinicopathological parameters, recurrence, locoregional and distant metastasis in 115 T1-T2 oral squamous cell carcinoma patients[J]. Head Neck Oncol, 2010, 2: 9.
3 Darwin D, Castelino RL, Babu GS, et al. Oral equilibrium in cachexia[J]. Asia Pac J Oncol Nurs, 2021, 8(5): 519-526.
4 Kim JM, Lin CJ, Stavre Z, et al. Osteoblast-osteoclast communication and bone homeostasis[J]. Cells, 2020, 9(9): 2073.
5 Yahara Y, Nguyen T, Ishikawa K, et al. The origins and roles of osteoclasts in bone development, homeostasis and repair[J]. Development, 2022, 149(8): dev199908.
6 Ambrosi TH, Marecic O, McArdle A, et al. Aged skeletal stem cells generate an inflammatory dege-nerative niche[J]. Nature, 2021, 597(7875): 256-262.
7 Cawley KM, Bustamante-Gomez NC, Guha AG, et al. Local production of osteoprotegerin by osteoblasts suppresses bone resorption[J]. Cell Rep, 2020, 32(10): 108052.
8 Zhu GY, Zhang TX, Chen M, et al. Bone physiological microenvironment and healing mechanism: basis for future bone-tissue engineering scaffolds[J]. Bioact Mater, 2021, 6(11): 4110-4140.
9 Arron JR, Choi Y. Bone versus immune system[J]. Nature, 2000, 408(6812): 535-536.
10 Zhu XZ, Huang HY, Zhao L. PAMPs and DAMPs as the bridge between periodontitis and atherosclerosis: the potential therapeutic targets[J]. Front Cell Dev Biol, 2022, 10: 856118.
11 Merle NS, Church SE, Fremeaux-Bacchi V, et al. Complement system part Ⅰ-molecular mechanisms of activation and regulation[J]. Front Immunol, 2015, 6: 262.
12 Sansores-España LD, Melgar-Rodríguez S, Vernal R, et al. Neutrophil N1 and N2 subsets and their possible association with periodontitis: a scoping review[J]. Int J Mol Sci, 2022, 23(20): 12068.
13 Jiang QS, Zhao YX, Shui YS, et al. Interactions between neutrophils and periodontal pathogens in late-onset periodontitis[J]. Front Cell Infect Microbiol, 2021, 11: 627328.
14 Wang JY, Zhou YC, Ren B, et al. The role of neutrophil extracellular traps in periodontitis[J]. Front Cell Infect Microbiol, 2021, 11: 639144.
15 Hajishengallis G. New developments in neutrophil biology and periodontitis[J]. Periodontol 2000, 2020, 82(1): 78-92.
16 Cortez A, Muxfeldt E. Monocyte chemoattractant protein-1 and hypertension: an overview[J]. Hiper-tens Riesgo Vasc, 2022, 39(1): 14-23.
17 Fazzalari NL. Bone fracture and bone fracture repair[J]. Osteoporos Int, 2011, 22(6): 2003-2006.
18 Cho TJ, Gerstenfeld LC, Einhorn TA. Differential temporal expression of members of the transfor-ming growth factor beta superfamily during murine fracture healing[J]. J Bone Miner Res, 2002, 17(3): 513-520.
19 Schultze JL, Schmidt SV. Molecular features of macrophage activation[J]. Semin Immunol, 2015, 27(6): 416-423.
20 Schlundt C, Fischer H, Bucher CH, et al. The multifaceted roles of macrophages in bone regeneration: a story of polarization, activation and time[J]. Acta Biomater, 2021, 133: 46-57.
21 Zhang B, Yang Y, Yi JR, et al. Hyperglycemia modulates M1/M2 macrophage polarization via reactive oxygen species overproduction in ligature-induced periodontitis[J]. J Periodontal Res, 2021, 56(5): 991-1005.
22 Chen M, Lin WM, Ye R, et al. PPARβ/δ agonist alleviates diabetic osteoporosis via regulating M1/M2 macrophage polarization[J]. Front Cell Dev Biol, 2021, 9: 753194.
23 Liu SC, Liu WL, Yang QF, et al. Non-coding-RNA-activated core/chitosan shell nanounits coated with polyetheretherketone for promoting bone regeneration and osseointegration via osteoimmunology[J]. ACS Appl Mater Interfaces, 2023, 15(10): 12653-12668.
24 Qiao D, Cheng SY, Xing Z, et al. Bio-inspired glycosylated nano-hydroxyapatites enhance endogenous bone regeneration by modulating macrophage M2 polarization[J]. Acta Biomater, 2023, 162: 135-148.
25 Wang JJ, Wang YZ, Li Y, et al. Unique regulation of TiO2 nanoporous topography on macrophage pola-rization via MSC-derived exosomes[J]. Regen Biomater, 2023, 10: rbad012.
26 Takayanagi H. Osteoimmunology and the effects of the immune system on bone[J]. Nat Rev Rheumatol, 2009, 5(12): 667-676.
27 Campbell L, Millhouse E, Malcolm J, et al. T cells, teeth and tissue destruction-what do T cells do in periodontal disease[J]. Mol Oral Microbiol, 2016, 31(6): 445-456.
28 Dar HY, Azam Z, Anupam R, et al. Osteoimmunology: the Nexus between bone and immune system[J]. Front Biosci, 2018, 23(3): 464-492.
29 Díaz-Zúñiga J, Melgar-Rodríguez S, Alvarez C, et al. T-lymphocyte phenotype and function triggered by Aggregatibacter actinomycetemcomitans is serotype-dependent[J]. J Periodontal Res, 2015, 50(6): 824-835.
30 Sakaguchi S, Yamaguchi T, Nomura T, et al. Regulatory T cells and immune tolerance[J]. Cell, 2008, 133(5): 775-787.
31 Sakaguchi S. Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses[J]. Annu Rev Immunol, 2004, 22: 531-562.
32 葛楠, 陈莉. Th17/Treg细胞平衡与骨代谢[J]. 北京口腔医学, 2018, 26(2): 114-117.
Ge N, Chen L. The balance of Th17/Treg cell and metabolism[J]. Beijing J Stomatol, 2018, 26(2): 114-117.
33 Chen K, Tang LY, Nong XL. Artesunate targets cellular metabolism to regulate the Th17/Treg cell ba-lance[J]. Inflamm Res, 2023, 72(5): 1037-1050.
34 Zhang SW, Gang XK, Yang S, et al. The alterations in and the role of the Th17/Treg balance in metabo-lic diseases[J]. Front Immunol, 2021, 12: 678355.
35 Zhou L, Lopes JE, Chong MMW, et al. TGF-beta-induced Foxp3 inhibits Th17 cell differentiation by antagonizing RORgammat function[J]. Nature, 2008, 453(7192): 236-240.
36 Michalek RD, Gerriets VA, Jacobs SR, et al. Cutting edge: distinct glycolytic and lipid oxidative metabo-lic programs are essential for effector and regulatory CD4+ T cell subsets[J]. J Immunol, 2011, 186(6): 3299-3303.
37 Feng Y, Chen Z, Tu SQ, et al. Role of interleukin-17A in the pathomechanisms of periodontitis and related systemic chronic inflammatory diseases[J]. Front Immunol, 2022, 13: 862415.
38 Zhang Y, Chen JY, Fu HJ, et al. Exosomes derived from 3D-cultured MSCs improve therapeutic effects in periodontitis and experimental colitis and restore the Th17 cell/Treg balance in inflamed periodontium[J]. Int J Oral Sci, 2021, 13(1): 43.
39 Cafferata EA, Jerez A, Vernal R, et al. The therapeutic potential of regulatory T lymphocytes in perio-dontitis: a systematic review[J]. J Periodontal Res, 2019, 54(3): 207-217.
40 Huang F, Wong P, Li JL, et al. Osteoimmunology: the correlation between osteoclasts and the Th17/Treg balance in osteoporosis[J]. J Cell Mol Med, 2022, 26(13): 3591-3597.
41 Zhu L, Hua F, Ding WG, et al. The correlation between the Th17/Treg cell balance and bone health[J]. Immun Ageing, 2020, 17: 30.
42 Giro G, Tebar A, Franco L, et al. Treg and TH17 link to immune response in individuals with peri-implantitis: a preliminary report[J]. Clin Oral Investig, 2021, 25(3): 1291-1297.
43 Yin JJ, Fang YR, Liao YY, et al. Bioinformatics investigation of adaptive immune-related genes in peri-implantitis and periodontitis: characteristics and diagnostic values[J]. Immun Inflamm Dis, 2024, 12(5): e1272.
44 Cafferata EA, Castro-Saavedra S, Fuentes-Barros G, et al. Boldine inhibits the alveolar bone resorption during ligature-induced periodontitis by modulating the Th17/Treg imbalance[J]. J Periodontol, 2021, 92(1): 123-136.
45 Cafferata EA, Terraza-Aguirre C, Barrera R, et al. Interleukin-35 inhibits alveolar bone resorption by modulating the Th17/Treg imbalance during perio-dontitis[J]. J Clin Periodontol, 2020, 47(6): 676-688.
46 Cheng WC, Hughes FJ, Taams LS. The presence, function and regulation of IL-17 and Th17 cells in periodontitis[J]. J Clin Periodontol, 2014, 41(6): 541-549.
47 Sato K, Suematsu A, Okamoto K, et al. Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction[J]. J Exp Med, 2006, 203(12): 2673-2682.
48 Langrish CL, Chen Y, Blumenschein WM, et al. IL-23 drives a pathogenic T cell population that indu-ces autoimmune inflammation[J]. J Exp Med, 2005, 201(2): 233-240.
49 Park H, Li ZX, Yang XO, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17[J]. Nat Immunol, 2005, 6(11): 1133-1141.
50 Jung S, Lee S, Kim HJ, et al. Mesenchymal stem cell-derived extracellular vesicles subvert Th17 cells by destabilizing RORγt through posttranslational modification[J]. Exp Mol Med, 2023, 55(3): 665-679.
51 Lee Y. The role of interleukin-17 in bone metabolism and inflammatory skeletal diseases[J]. BMB Rep, 2013, 46(10): 479-483.
52 Gaffen SL, Moutsopoulos NM. Regulation of host-microbe interactions at oral mucosal barriers by type 17 immunity[J]. Sci Immunol, 2020, 5(43): eaau4594.
53 Liu SC, Hsieh HL, Tsai CH, et al. CCN2 facilitates IL-17 production and osteoclastogenesis in human osteoarthritis synovial fibroblasts by inhibiting miR-655 expression[J]. J Bone Miner Res, 2022, 37(10): 1944-1955.
54 Vernal R, Díaz-Zúñiga J, Melgar-Rodríguez S, et al. Activation of RANKL-induced osteoclasts and me-mory T lymphocytes by Porphyromonas gingivalis is serotype dependant[J]. J Clin Periodontol, 2014, 41(5): 451-459.
55 Ono T, Takayanagi H. Osteoimmunology in bone fracture healing[J]. Curr Osteoporos Rep, 2017, 15(4): 367-375.
56 Adamopoulos IE, Chao CC, Geissler R, et al. Interleukin-17A upregulates receptor activator of NF-kappaB on osteoclast precursors[J]. Arthritis Res Ther, 2010, 12(1): R29.
57 Kim HJ, Seo SJ, Kim JY, et al. IL-17 promotes osteoblast differentiation, bone regeneration, and remodeling in mice[J]. Biochem Biophys Res Commun, 2020, 524(4): 1044-1050.
58 Zhao XM, Liu WJ, Wu ZC, et al. Hepatocyte growth factor is protective in early stage but bone-destructive in late stage of experimental periodontitis[J]. J Periodontal Res, 2024, 59(3): 565-575.
59 Li GH, Liu L, Yin ZH, et al. Glutamine metabolism is essential for the production of IL-17A in γδ T cells and skin inflammation[J]. Tissue Cell, 2021, 71: 101569.
60 Peng RP, Dong YM, Zheng M, et al. IL-17 promotes osteoclast-induced bone loss by regulating glutamine-dependent energy metabolism[J]. Cell Death Dis, 2024, 15(2): 111.
61 Ono T, Okamoto K, Nakashima T, et al. IL-17-producing γδ T cells enhance bone regeneration[J]. Nat Commun, 2016, 7: 10928.
62 Nam D, Mau E, Wang YF, et al. T-lymphocytes ena-ble osteoblast maturation via IL-17F during the early phase of fracture repair[J]. PLoS One, 2012, 7(6): e40044.
63 Huang H, Kim HJ, Chang EJ, et al. IL-17 stimulates the proliferation and differentiation of human me-senchymal stem cells: implications for bone remode-ling[J]. Cell Death Differ, 2009, 16(10): 1332-1343.
64 McInnes IB, Mease PJ, Kirkham B, et al. Secukinu-mab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial[J]. Lancet, 2015, 386(9999): 1137-1146.
65 Baeten D, Baraliakos X, Braun J, et al. Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial[J]. Lancet, 2013, 382(9906): 1705-1713.
66 Liao CS, Zhang CF, Jin LJ, et al. IL-17 alters the mesenchymal stem cell niche towards osteogenesis in cooperation with osteocytes[J]. J Cell Physiol, 2020, 235(5): 4466-4480.
67 Bao JQ, Wang ZX, Yang YT, et al. Interleukin-17 alleviates erastin-induced alveolar bone loss by suppressing ferroptosis via interaction between NRF2 and p-STAT3[J]. J Clin Periodontol, 2024, 51(2): 233-250.
68 Kim YG, Park JW, Lee JM, et al. IL-17 inhibits osteoblast differentiation and bone regeneration in rat[J]. Arch Oral Biol, 2014, 59(9): 897-905.
69 Gaffen SL. Structure and signalling in the IL-17 receptor family[J]. Nat Rev Immunol, 2009, 9(8): 556-567.
70 Raphael I, Nalawade S, Eagar TN, et al. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases[J]. Cytokine, 2015, 74(1): 5-17.
71 Lam J, Takeshita S, Barker JE, et al. TNF-alpha induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand[J]. J Clin Invest, 2000, 106(12): 1481-1488.
72 Zhang WJ, Dang K, Huai Y, et al. Osteoimmunology: the regulatory roles of T lymphocytes in osteoporosis[J]. Front Endocrinol, 2020, 11: 465.
73 Li SS, Yin YX, Yao LP, et al. TNF‑α treatment increases DKK1 protein levels in primary osteoblasts via upregulation of DKK1 mRNA levels and downregulation of miR-335-5p[J]. Mol Med Rep, 2020, 22(2): 1017-1025.
74 Diarra D, Stolina M, Polzer K, et al. Dickkopf-1 is a master regulator of joint remodeling[J]. Nat Med, 2007, 13(2): 156-163.
75 Du D, Zhou ZB, Zhu L, et al. TNF-α suppresses osteogenic differentiation of MSCs by accelerating P2Y2 receptor in estrogen-deficiency induced osteoporosis[J]. Bone, 2018, 117: 161-170.
76 Rossi M, Rana I, Buonuomo PS, et al. Stimulation of Treg cells to inhibit osteoclastogenesis in gorham-stout disease[J]. Front Cell Dev Biol, 2021, 9: 706596.
77 Torres-Monjarás AP, Sánchez-Gutiérrez R, Her-nández-Castro B, et al. Bacteria associated with apical periodontitis promotes in vitro the differentiation of macrophages to osteoclasts[J]. Clin Oral Investig, 2023, 27(6): 3139-3148.
78 von Kaeppler EP, Wang Q, Raghu H, et al. Interleukin 4 promotes anti-inflammatory macrophages that clear cartilage debris and inhibits osteoclast development to protect against osteoarthritis[J]. Clin Immunol, 2021, 229: 108784.
79 Okamoto K, Nakashima T, Shinohara M, et al. Osteoimmunology: the conceptual framework unifying the immune and skeletal systems[J]. Physiol Rev, 2017, 97(4): 1295-1349.
80 Oi K, Tokunaga T, Kuranobu T, et al. Tumour necrosis factor α augments the inhibitory effects of CTLA-4-Ig on osteoclast generation from human monocytes via induction of CD80 expression[J]. Clin Exp Immunol, 2019, 196(3): 392-402.
81 Houde N, Chamoux E, Bisson M, et al. Transfor-ming growth factor-beta1 (TGF-beta1) induces human osteoclast apoptosis by up-regulating Bim[J]. J Biol Chem, 2009, 284(35): 23397-23404.
82 Xia YH, Inoue K, Du Y, et al. TGFβ reprograms TNF stimulation of macrophages towards a non-canonical pathway driving inflammatory osteoclastogenesis[J]. Nat Commun, 2022, 13(1): 3920.
83 Yasui T, Kadono Y, Nakamura M, et al. Regulation of RANKL-induced osteoclastogenesis by TGF‑β through molecular interaction between Smad3 and Traf6[J]. J Bone Miner Res, 2011, 26(7): 1447-1456.
84 Kaneda T, Nojima T, Nakagawa M, et al. Endogenous production of TGF-beta is essential for osteoclastogenesis induced by a combination of receptor activator of NF-kappa B ligand and macrophage-co-lony-stimulating factor[J]. J Immunol, 2000, 165(8): 4254-4263.
85 Lee B, Oh Y, Jo S, et al. A dual role of TGF-β in human osteoclast differentiation mediated by Smad1 versus Smad3 signaling[J]. Immunol Lett, 2019, 206: 33-40.
86 Richardson L, Wilcockson SG, Guglielmi L, et al. Context-dependent TGFβ family signalling in cell fate regulation[J]. Nat Rev Mol Cell Biol, 2023, 24(12): 876-894.
87 Quinn JM, Itoh K, Udagawa N, et al. Transforming growth factor beta affects osteoclast differentiation via direct and indirect actions[J]. J Bone Miner Res, 2001, 16(10): 1787-1794.
88 Karst M, Gorny G, Galvin RJ, et al. Roles of stromal cell RANKL, OPG, and M-CSF expression in biphasic TGF-beta regulation of osteoclast differentiation[J]. J Cell Physiol, 2004, 200(1): 99-106.
89 Tanaka Y. Clinical immunity in bone and joints[J]. J Bone Miner Metab, 2019, 37(1): 2-8.
90 Runyan CE, Liu ZY, William Schnaper H. Phosphatidylinositol 3-kinase and Rab5 GTPase inversely regulate the Smad anchor for receptor activation (SARA) protein independently of transforming grow-th factor-β1[J]. J Biol Chem, 2012, 287(43): 35815-35824.
91 Zhao LM, Jiang S, Hantash BM. Transforming growth factor beta1 induces osteogenic differentiation of murine bone marrow stromal cells[J]. Tissue Eng Part A, 2010, 16(2): 725-733.
92 Jann J, Gascon S, Roux S, et al. Influence of the TGF‑β superfamily on osteoclasts/osteoblasts ba-lance in physiological and pathological bone conditions[J]. Int J Mol Sci, 2020, 21(20): 7597.
93 Zhang ZD, Zhang XZ, Zhao DW, et al. TGF-β1 promotes the osteoinduction of human osteoblasts via the PI3K/AKT/mTOR/S6K1 signalling pathway[J]. Mol Med Rep, 2019, 19(5): 3505-3518.
94 Yu MC, D’Amelio P, Tyagi AM, et al. Regulatory T cells are expanded by Teriparatide treatment in humans and mediate intermittent PTH-induced bone anabolism in mice[J]. EMBO Rep, 2018, 19(1): 156-171.
95 Tyagi AM, Yu MC, Darby TM, et al. The microbial metabolite butyrate stimulates bone formation via T regulatory cell-mediated regulation of WNT10B expression[J]. Immunity, 2018, 49(6): 1116-1131.e7.
96 Li CC, Bi W, Gong YM, et al. Transforming growth factor-beta1 inhibits tissue engineering cartilage absorption via inducing the generation of regulatory T cells[J]. J Tissue Eng Regen Med, 2016, 10(2): E113-E120.
97 Lin YF, Wang ZY, Liu SR, et al. Roles of extracellular vesicles on macrophages in inflammatory bone diseases[J]. Mol Cell Biochem, 2024, 479(6): 1401-1414.
98 Gu YZ, Han XZ. Toll-like receptor signaling and immune regulatory lymphocytes in periodontal disease[J]. Int J Mol Sci, 2020, 21(9): 3329.
99 Li RM, Zhu ZY, Zhang BL, et al. Manganese enhances the osteogenic effect of silicon-hydroxyapatite nanowires by targeting T lymphocyte polarization[J]. Adv Sci, 2024, 11(4): e2305890.
100 Fox S, Leitch AE, Duffin R, et al. Neutrophil apoptosis: relevance to the innate immune response and inflammatory disease[J]. J Innate Immun, 2010, 2(3): 216-227.
101 Wang XX, Sun B, Wang YJ, et al. Research pro-gress of targeted therapy regulating Th17/Treg ba-lance in bone immune diseases[J]. Front Immunol, 2024, 15: 1333993.
102 Deng JW, Lu CT, Zhao QT, et al. The Th17/Treg cell balance: crosstalk among the immune system, bone and microbes in periodontitis[J]. J Periodontal Res, 2022, 57(2): 246-255.
103 周剑鹏, 谢旭东, 赵蕾, 等. 辅助性T细胞17及白细胞介素17在牙周炎中的作用及机制的研究进展[J]. 国际口腔医学杂志, 2022, 42(5): 586-592.
Zhou JP, Xie XD, Zhao L, et al. Research progress on the roles and mechanisms of T-helper 17 cells and interleukin-17 in periodontitis[J]. Int J Stomatol, 2022, 42(5): 586-592.
104 吕辉, 王华, 孙雯. 辅助性T细胞17与牙周炎骨免疫[J]. 国际口腔医学杂志, 2020, 47(6): 661-668.
Lü H, Wang H, Sun W. T helper cell 17 and perio-dontitis related osteoimmunology[J]. Int J Stomatol, 2020, 47(6): 661-668.
105 张黎, 刘育菘, 吴芸菲, 等. 壳寡糖对牙周炎大鼠牙槽骨吸收及Th17/Treg平衡和OPG/RANKL/RANK通路的影响[J]. 上海口腔医学, 2021, 30(3): 237-242.
Zhang L, Liu YS, Wu YF, et al. Effects of chitosan oligosaccharide on alveolar bone resorption, Th17/Treg balance and OPG/RANKL/RANK pathway in periodontitis rats[J]. Shanghai J Stomatol, 2021, 30(3): 237-242.
106 Schipani E, Maes C, Carmeliet G, et al. Regulation of osteogenesis-angiogenesis coupling by HIFs and VEGF[J]. J Bone Miner Res, 2009, 24(8): 1347-1353.
107 Athanasopoulos AN, Schneider D, Keiper T, et al. Vascular endothelial growth factor (VEGF)-induced up-regulation of CCN1 in osteoblasts mediates proangiogenic activities in endothelial cells and promotes fracture healing[J]. J Biol Chem, 2007, 282(37): 26746-26753.
108 Nagai K, Ideguchi H, Kajikawa T, et al. An injectable hydrogel-formulated inhibitor of prolyl-4-hydroxylase promotes T regulatory cell recruitment and enhances alveolar bone regeneration during re-solution of experimental periodontitis[J]. FASEB J, 2020, 34(10): 13726-13740.
109 Elashiry M, Elashiry MM, Elsayed R, et al. Dendri-tic cell derived exosomes loaded with immunoregulatory cargo reprogram local immune responses and inhibit degenerative bone disease in vivo [J]. J Extracell Vesicles, 2020, 9(1): 1795362.
110 Henin D, Fiorin LG, Carmagnola D, et al. Quantitative evaluation of inflammatory markers in peri-implantitis and periodontitis tissues: digital vs. manual analysis-a proof of concept study[J]. Medicina, 2022, 58(7): 867.
111 黄萧瑜, 李明云, 周学东, 等. 全身及局部因素对种植体周围稳态的影响[J]. 国际口腔医学杂志, 2019, 46(6): 730-734.
Huang XY, Li MY, Zhou XD, et al. Effects of systemic and local factors on microbial homeostasis around implants[J]. Int J Stomatol, 2019, 46(6): 730-734.
112 Cha JK, Lee JS, Kim CS. Surgical therapy of peri-implantitis with local minocycline: a 6-month randomized controlled clinical trial[J]. J Dent Res, 2019, 98(3): 288-295.
113 Tarnow DP. Increasing prevalence of peri-implantitis: how will we manage[J]. J Dent Res, 2016, 95(1): 7-8.
114 Liu XC, Deng SD, Xie JX, et al. 2-DG regulates immune imbalance on the titanium surface after debridement[J]. Int J Mol Sci, 2023, 24(14): 11431.
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