Int J Stomatol

Int J Stomatol ›› 2022, Vol. 49 ›› Issue (5): 593-599.doi: 10.7518/gjkq.2022085

• Reviews • Previous Articles     Next Articles

Progress in understanding the correlations between semaphorin 3A and common oral diseases

Chen Huiyu(),Bai Mingru,Ye Ling.()   

  1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
  • Received:2021-12-06 Revised:2022-04-06 Online:2022-09-01 Published:2022-09-16
  • Contact: Ling. Ye E-mail:417823395@qq.com;1034194884@qq.com
  • Supported by:
    National Natural Science Foundation of China Youth Science Foundation(82001020)

RichHTML

17

PDF (PC)

396

Abstract:

Semaphorin 3A (Sema3A) is a membrane-associated secreted protein produced by endothelial cells that regulate vascularization, cancer progression, bone biology, and immune homeostasis. Oral diseases are common and frequently occur in the human body. In recent years, an increasing number of studies have found that Sema3A expression changes with the progression of some common oral diseases. Sema3A inhibits apical periodontitis and pulpitis by inhibiting the expression of pro-inflammatory mediators to repress inflammation. In addition, it can also compete with vascular endothelial growth factors to bind its receptors to inhibit tumor angiogenesis. Oral diseases are represented by pulpitis, periodontitis, periapical periodontitis, dental dysplasia, and oral cancer. Exploring the role of Sema3A in oral diseases is of far-reaching significance for the comprehensive analysis of the molecular mechanisms in the diseases and the development of therapeutic drugs for intervention and treatment methods. In this paper, we will discuss the correlations between Sema3A and oral diseases and their molecular mechanisms.

Key words: semaphorin 3A, pulpitis, apical periodontitis, periodontitis, dental dysplasia, oral cancer

CLC Number: 

  • R 78

TrendMD: 
1 Kapila YL. Oral health’s inextricable connection to systemic health: special populations bring to bear multimodal relationships and factors connecting periodontal disease to systemic diseases and conditions[J]. Periodontol 2000, 2021, 87(1): 11-16.
2 Vergnes JN, Mazevet M. Oral diseases: a global public health challenge[J]. Lancet, 2020, 395(10219): 186.
3 Yoshida S, Wada N, Hasegawa D, et al. Semaphorin 3A induces odontoblastic phenotype in dental pulp stem cells[J]. J Dent Res, 2016, 95(11): 1282-1290.
4 Lin Y, Xing Q, Qin W, et al. Decreased expression of Semaphorin3A/neuropilin-1 signaling axis in apical periodontitis[J]. Biomed Res Int, 2017, 2017: 8724503.
5 Ni QW, Sun JL, Ma C, et al. The neuropilins and their ligands in hematogenous metastasis of salivary adenoid cystic carcinoma-an immunohistochemical study[J]. J Oral Maxillofac Surg, 2018, 76(3): 569-579.
6 Duncan HF, Cooper PR. Pulp innate immune defense: translational opportunities[J]. J Endod, 2020, 46(9S): S10-S18.
7 Ribeiro-Santos FR, Arnez MFM, de Carvalho MS, et al. Effect of non-steroidal anti-inflammatory drugs on pulpal and periapical inflammation induced by lipopolysaccharide[J]. Clin Oral Investig, 2021, 25(11): 6201-6209.
8 Giraud T, Jeanneau C, Rombouts C, et al. Pulp capping materials modulate the balance between inflammation and regeneration[J]. Dent Mater, 2019, 35(1): 24-35.
9 Shindo S, Kumagai T, Shirawachi S, et al. Semaphorin3A released from human dental pulp cells inhibits the increase in interleukin-6 and CXC chemokine ligand 10 production induced by tumor necrosis factor-α through suppression of nuclear factor-κB activation[J]. Cell Biol Int, 2021, 45(1): 238-244.
10 Song YH, Liu XJ, Feng XM, et al. NRP1 accelerates odontoblast differentiation of dental pulp stem cells through classical wnt/β-catenin signaling[J]. Cell Reprogram, 2017, 19(5): 324-330.
11 Wang CF, Song YH, Gu ZF, et al. Wedelolactone enhances odontoblast differentiation by promoting wnt/β‑catenin signaling pathway and suppressing NF-κB signaling pathway[J]. Cell Reprogram, 2018, 20(4): 236-244.
12 Xiong H, Wei L, Peng B. The Presence and involvement of interleukin-17 in apical periodontitis[J]. Int Endod J, 2019, 52(8): 1128-1137.
13 Yue JL, Song DZ, Lu WL, et al. Expression profiles of inflammation-associated microRNAs in periapical lesions and human periodontal ligament fibroblasts inflammation[J]. J Endod, 2016, 42(12): 1773-1778.
14 Adi SD, Eiza N, Bejar J, et al. Semaphorin 3A is effective in reducing both inflammation and angiogenesis in a mouse model of bronchial asthma[J]. Front Immunol, 2019, 10: 550.
15 Catalano A. The neuroimmune semaphorin-3A reduces inflammation and progression of experimental autoimmune arthritis[J]. J Immunol, 2010, 185(10): 6373-6383.
16 Nishide M, Kumanogoh A. The role of semaphorins in immune responses and autoimmune rheumatic diseases[J]. Nat Rev Rheumatol, 2018, 14(1): 19-31.
17 Hayashi M, Nakashima T, Taniguchi M, et al. Osteoprotection by semaphorin 3A[J]. Nature, 2012, 485(7396): 69-74.
18 Li ZX, Hao J, Duan X, et al. The role of semaphorin 3A in bone remodeling[J]. Front Cell Neurosci, 2017, 11: 40.
19 Pan WY, Wang QX, Chen QM. The cytokine network involved in the host immune response to periodontitis[J]. Int J Oral Sci, 2019, 11(3): 30.
20 李亚萍, 蔡同道. 慢性牙周炎龈沟液中Sema3A/Nrp1通路与炎症反应、骨质破坏的相关性研究[J]. 海南医学院学报, 2017, 23(19): 2739-2741.
Li YP, Cai TD. Correlation of Sema3A/Nrp1 pathway in gingival crevicular fluid of chronic periodontitis with inflammatory response and bone destruction[J]. J Hainan Med Univ, 2017, 23(19): 2739-2741.
21 Rienks M, Carai P, Bitsch N, et al. Sema3A promotes the resolution of cardiac inflammation after myocardial infarction[J]. Basic Res Cardiol, 2017, 112(4): 42.
22 Wen HT, Lei Y, Eun SY, et al. Plexin-A4-semaphorin 3A signaling is required for Toll-like receptor- and sepsis-induced cytokine storm[J]. J Exp Med, 2010, 207(13): 2943-2957.
23 Murray PJ. Macrophage polarization[J]. Annu Rev Physiol, 2017, 79: 541-566.
24 Yang JM, Zhu Y, Duan DY, et al. Enhanced activity of macrophage M1/M2 phenotypes in periodontitis[J]. Arch Oral Biol, 2018, 96: 234-242.
25 Yu T, Zhao L, Huang X, et al. Enhanced activity of the macrophage M1/M2 phenotypes and phenotypic switch to M1 in periodontal infection[J]. J Periodontol, 2016, 87(9): 1092-1102.
26 Hayashi M, Nakashima T, Yoshimura N, et al. Autoregulation of osteocyte Sema3A orchestrates estrogen action and counteracts bone aging[J]. Cell Metab, 2019, 29(3): 627-637.e5.
27 Xu XR, Fang KX, Wang LF, et al. Local application of semaphorin 3A combined with adipose-derived stem cell sheet and anorganic bovine bone granules enhances bone regeneration in type 2 diabetes mellitus rats[J]. Stem Cells Int, 2019, 2019: 2506463.
28 Maeda H. Mass acquisition of human periodontal ligament stem cells[J]. World J Stem Cells, 2020, 12(9): 1023-1031.
29 Tomokiyo A, Wada N, Maeda H. Periodontal ligament stem cells: regenerative potency in periodontium[J]. Stem Cells Dev, 2019, 28(15): 974-985.
30 Tian T, Tang KL, Wang AQ, et al. The effects of Sema3A overexpression on the proliferation and differentiation of rat gingival mesenchymal stem cells in the LPS-induced inflammatory environment[J]. Int J Clin Exp Pathol, 2019, 12(10): 3710-3718.
31 Wada N, Maeda H, Hasegawa D, et al. Semaphorin 3A induces mesenchymal-stem-like properties in human periodontal ligament cells[J]. Stem Cells Dev, 2014, 23(18): 2225-2236.
32 Niftullayev S, Lamarche-Vane N. Regulators of rho GTPases in the nervous system: molecular implication in axon guidance and neurological disorders[J]. Int J Mol Sci, 2019, 20(6): E1497.
33 Luo Y, Raible D, Raper JA. Collapsin: a protein in brain that induces the collapse and paralysis of neuronal growth cones[J]. Cell, 1993, 75(2): 217-227.
34 Lee H, MacPherson LJ, Parada CA, et al. Rewiring the taste system[J]. Nature, 2017, 548(7667): 330-333.
35 Jitsuki-Takahashi A, Jitsuki S, Yamashita N, et al. Activity-induced secretion of semaphorin 3A mediates learning[J]. Eur J Neurosci, 2021, 53(10): 3279-3293.
36 Liu AQ, Zhang LS, Fei DD, et al. Sensory nerve-deficient microenvironment impairs tooth homeostasis by inducing apoptosis of dental pulp stem cells[J]. Cell Prolif, 2020, 53(5): e12803.
37 Løes S, Kettunen P, Kvinnsland IH, et al. Expression of class 3 semaphorins and neuropilin receptors in the developing mouse tooth[J]. Mech Dev, 2001, 101(1/2): 191-194.
38 Kettunen P, Løes S, Furmanek T, et al. Coordination of trigeminal axon navigation and patterning with tooth organ formation: epithelial-mesenchymal interactions, and epithelial Wnt4 and Tgfbeta1 regulate semaphorin 3a expression in the dental mesenchyme[J]. Development, 2005, 132(2): 323-334.
39 Fujii S, Nagata K, Matsumoto S, et al. Wnt/β‑catenin signaling, which is activated in odontomas, reduces Sema3A expression to regulate odontogenic epithelial cell proliferation and tooth germ development[J]. Sci Rep, 2019, 9(1): 4257.
40 Yu XJ, Zheng FJ, Du Y, et al. Semaphorin 3A gets involved in the establishment of mouse tooth eruptive pathway[J]. J Mol Histol, 2019, 50(5): 427-434.
41 Narematsu M, Kamimura T, Yamagishi T, et al. Hypoxia-induced downregulation of Sema3a and CXCL12/CXCR4 regulate the formation of the coronary artery stem at the proper site[J]. J Mol Cell Cardiol, 2020, 147: 62-73.
42 Cerani A, Tetreault N, Menard C, et al. Neuron-derived semaphorin 3A is an early inducer of vascular permeability in diabetic retinopathy via neuropilin-1[J]. Cell Metab, 2013, 18(4): 505-518.
43 Osada R, Horiuchi A, Kikuchi N, et al. Expression of semaphorins, vascular endothelial growth factor, and their common receptor neuropilins and alleic loss of semaphorin locus in epithelial ovarian neoplasms: increased ratio of vascular endothelial growth factor to semaphorin is a poor prognostic factor in ovarian carcinomas[J]. Hum Pathol, 2006, 37(11): 1414-1425.
44 Lavi N, Kessler O, Ziv K, et al. Semaphorin-3A inhibits multiple myeloma progression in a mouse model[J]. Carcinogenesis, 2018, 39(10): 1283-1291.
45 Casazza A, Laoui D, Wenes M, et al. Impeding macrophage entry into hypoxic tumor areas by Sema3A/Nrp1 signaling blockade inhibits angiogenesis and restores antitumor immunity[J]. Cancer Cell, 2013, 24(6): 695-709.
46 Liu LN, Li XM, Ye DQ, et al. Emerging role of semaphorin-3A in autoimmune diseases[J]. Inflammopharmacology, 2018, 26(3): 655-665.
47 Huang C, Wang Y, Huang JH, et al. Sema3A drastically suppresses tumor growth in oral cancer xenograft model of mice[J]. BMC Pharmacol Toxicol, 2017, 18(1): 55.
48 Wang Z, Chen J, Zhang W, et al. Axon guidance molecule semaphorin3A is a novel tumor suppressor in head and neck squamous cell carcinoma[J]. Oncotarget, 2016, 7(5): 6048-6062.
49 Shahrabi-Farahani S, Gallottini M, Martins F, et al. Neuropilin 1 receptor is up-regulated in dysplastic epithelium and oral squamous cell carcinoma[J]. Am J Pathol, 2016, 186(4): 1055-1064.
50 Song X, Zhang W, Zhang Y, et al. Expression of semaphorin 3A and neuropilin 1 with clinicopathological features and survival in human tongue cancer[J]. Med Oral Patol Oral Cir Bucal, 2012, 17(6): e962-e968.
51 李胜男, 查小雨, 张杰, 等. 涎腺黏液表皮样癌组织SEMA3A与SEMA3B及p53表达临床意义[J]. 中华肿瘤防治杂志, 2018, 25(14): 997-1002.
Li SN, Zha XY, Zhang J, et al. Prognostic prediction role of SEMA3A, SEMA3B and p53 proteins in mucoepidermal carcinoma of salivary gland[J]. Chin J Cancer Prev Treat, 2018, 25(14): 997-1002.
[1] Fu Yu, He Wei, Huang Lan. Ferroptosis and its implication in oral diseases [J]. Int J Stomatol, 2024, 51(1): 36-44.
[2] Luo Xiaojie,Wang Dexu,Chen Xiaotao. Relationship between periodontitis and ferroptosis based on bioinformatics analysis [J]. Int J Stomatol, 2023, 50(6): 661-668.
[3] Huang Yuanhong,Peng Xian,Zhou Xuedong.. Progress in research into the effect of Rhizoma Drynariae on the treatment of bone-related diseases in the oral cavity [J]. Int J Stomatol, 2023, 50(6): 679-685.
[4] Hu Jia,Wang Xiuqing,Lu Guoying,Huang Xiaojing.. Regenerative endodontic procedures for permanent tooth with immature apices in adult patients [J]. Int J Stomatol, 2023, 50(6): 686-695.
[5] Gong Meiling,Cheng Xingqun,Wu Hongkun.. Research progress on the correlation between Parkinson’s disease and periodontitis [J]. Int J Stomatol, 2023, 50(5): 587-593.
[6] Xu Zhibo,Meng Xiuping.. Research progress on mechanism of Enterococcus faecalis escaping host immune defense [J]. Int J Stomatol, 2023, 50(5): 613-617.
[7] Jiang Yueying,He Yutian,Li Ting,Zhou Ronghui.. Research progress on the application of near infrared fluorescence probe in the diagnosis of oral cancer [J]. Int J Stomatol, 2023, 50(4): 407-413.
[8] Fan Lin,Sun Jiang.. Application of microneedles in stomatology [J]. Int J Stomatol, 2023, 50(4): 472-478.
[9] Sun Jia,Han Ye,Hou Jianxia. Research progress on the role of interleukin-6-hepcidin signal axis in regulating the pathogenesis of periodontitis-associated anemia [J]. Int J Stomatol, 2023, 50(3): 329-334.
[10] Lin Huiping,Xu Ting,Lin Jun.. Research progress on artificial intelligence techniques in diagnosis of oral cancer and potentially malignant disorders [J]. Int J Stomatol, 2023, 50(2): 138-145.
[11] Liang Zhiying,Zhao Yuanxi,Zhu Jiani,Su Qin.. Retrospective analysis of clinical data of 288 cases of endodontic microsurgery on anterior teeth [J]. Int J Stomatol, 2023, 50(2): 166-171.
[12] Wang Taiping,Shi Xinglian,Li Zhezhen,Liu Mei,Jiang Jianhong. Analysis of psychological factors and intervention in patients with oral cancer [J]. Int J Stomatol, 2023, 50(2): 203-209.
[13] Liu Tiqian,Liang Xing,Liu Weiqing,Li Xiaohong,Zhu Rui.. Research progress on the role and mechanism of occlusal trauma in the development of periodontitis [J]. Int J Stomatol, 2023, 50(1): 19-24.
[14] Li Qiong,Yu Weixian. Research progress on resveratrol for the treatment of periodontitis and its bioavailability [J]. Int J Stomatol, 2023, 50(1): 25-31.
[15] Huang Weikun,Xu Qiuyan,Zhou Ting.. Role of baicalin and mechanisms through which baicalin attenuates oxidative stress injury induced by lipopolysaccharide on macrophages [J]. Int J Stomatol, 2022, 49(5): 521-528.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[2] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[3] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[4] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[5] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[6] . [J]. Foreign Med Sci: Stomatol, 1999, 26(04): .
[7] . [J]. Foreign Med Sci: Stomatol, 1999, 26(04): .
[8] . [J]. Foreign Med Sci: Stomatol, 1999, 26(04): .
[9] . [J]. Foreign Med Sci: Stomatol, 1999, 26(04): .
[10] . [J]. Foreign Med Sci: Stomatol, 1999, 26(04): .