国际口腔医学杂志 ›› 2024, Vol. 51 ›› Issue (3): 374-380.doi: 10.7518/gjkq.2024046

• 综述 • 上一篇    

同源盒基因调控先天缺牙的研究进展

张伟杰1(),刘向晖2,杨玉娥2()   

  1. 1.滨州医学院 烟台 264000
    2.青岛大学附属青岛市口腔医院儿童口腔科 青岛 266001
  • 收稿日期:2023-08-23 修回日期:2024-01-23 出版日期:2024-05-01 发布日期:2024-05-06
  • 通讯作者: 杨玉娥
  • 作者简介:张伟杰,医师,硕士,Email:<email>1379292653@qq.com</email>
  • 基金资助:
    青岛市医疗卫生重点学科建设项目(2022-2024 );青岛市口腔疾病临床医学研究中心项目(2021-2024)

Recent advances in regulation of congenitally absent teeth by homeobox genes

Weijie Zhang1(),Xianghui Liu2,Yu’e Yang2()   

  1. 1.Binzhou Medical University, Yantai 264000, China
    2.Dept. of Pediatric Dentistry, Qingdao Stomatological Hospital Affiliated to Qingdao University, Qingdao 266001, China
  • Received:2023-08-23 Revised:2024-01-23 Online:2024-05-01 Published:2024-05-06
  • Contact: Yu’e Yang
  • Supported by:
    Qingdao Key Health Discipline Development Fund (2022-2024);Qingdao Clinical Research Center for Oral Diseases Fund (2021-2024)

摘要:

同源盒基因是一个进化上高度保守的含有同源结构域的转录因子,其编码的转录调节因子在器官发生上起着重要的调控作用。该家族中的多个亚家族不仅参与了牙胚的分化过程,而且常由于其异常的表达导致先天缺牙的发生。随着分子遗传学、基因工程和人类基因组计划在先天缺牙疾病上的不断深入探索,同源盒基因突变类型及表达模式的研究正成为先天缺牙疾病的主要研究方向。本文通过对近年来文献回顾,对同源盒基因的研究进展、与先天缺牙相关同源盒基因的表达模式和分子机制以及同源盒基因在先天缺牙临床诊疗中的应用前景进行综述。

关键词: 同源盒基因, 先天缺牙, 非综合征性先天缺牙, 牙齿发育, 基因突变, 牙组织再生工程, 配对盒基因9, 肌节同源异型盒基因1

Abstract:

The homeobox gene is an evolutionarily conserved transcription factor containing homologous domain, and its encoded transcription regulatory factor plays an important role in organogenesis. Several subfamilies of the homeobox gene family are involved in the development of the maxillofacial region in vertebrates, and their abnormal expression is closely related to the occurrence of congenitally missing teeth. With the development of molecular genetics, genetic engineering, and human genome project, the study of newly discovered homeobox genes, mutation types, and expression patterns is becoming the main research direction of congenitally missing teeth diseases. This study reviews the literature on the latest research progress of homeobox genes in recent years, the expression patterns and molecular mechanisms of homeobox genes related to congenitally missing teeth, and the application prospect of homologous box gene in the clinical diagnosis and treatment of congenital missing teeth.

Key words: homeobox gene, congenitally missing teeth, nonsyndromic tooth agenesis, tooth development, gene mutation, dental tissue regeneration engineering, paired box 9, muscle segment homeobox gene 1

中图分类号: 

  • R781.9
1 Khalaf K, Miskelly J, Voge E, et al. Prevalence of hypodontia and associated factors: a systematic review and meta-analysis[J]. J Orthod, 2014, 41(4): 299-316.
2 Albu CC, Pavlovici RC, Imre M, et al. Research algorithm for the detection of genetic patterns and phenotypic variety of non-syndromic dental agenesis[J]. Rom J Morphol Embryol, 2021, 62(1): 53-62.
3 Kurosaka H, Itoh S, Morita C, et al. Development of dentition: from initiation to occlusion and related diseases[J]. J Oral Biosci, 2022, 64(2): 159-164.
4 Khan MI, Ahmed N, Neela PK, et al. The human genetics of dental anomalies[J]. Glob Med Genet, 2022, 9(2): 76-81.
5 Gopinathan G, Zhang XM, Luan XH, et al. Changes in Hox gene chromatin organization during odontogenic lineage specification[J]. Genes (Basel), 2023, 14(1): 198.
6 McGinnis W, Garber RL, Wirz J, et al. A homologous protein-coding sequence in Drosophila homeotic genes and its conservation in other metazoans[J]. Cell, 1984, 37(2): 403-408.
7 Akin ZN, Nazarali AJ. Hox genes and their candidate downstream targets in the developing central nervous system[J]. Cell Mol Neurobiol, 2005, 25(3/4): 697-741.
8 Jiménez-Mejía G, Montalvo-Méndez R, Hernández-Bautista C, et al. Trimeric complexes of Antp-TBP with TFIIEβ or Exd modulate transcriptional activity[J]. Hereditas, 2022, 159(1): 23.
9 Gaunt SJ. Hox cluster genes and collinearities th-roughout the tree of animal life[J]. Int J Dev Biol, 2018, 62(11/12): 673-683.
10 Bürglin TR, Affolter M. Homeodomain proteins: an update[J]. Chromosoma, 2016, 125(3): 497-521.
11 Fauzi NH, Ardini YD, Zainuddin Z, et al. A review on non-syndromic tooth agenesis associated with PAX9 mutations[J]. Jpn Dent Sci Rev, 2018, 54(1): 30-36.
12 Koskinen S, Keski-Filppula R, Alapulli H, et al. Familial oligodontia and regional odontodysplasia associated with a PAX9 initiation codon mutation[J]. Clin Oral Investig, 2019, 23(11): 4107-4111.
13 Fournier BP, Bruneau MH, Toupenay S, et al. Patterns of dental agenesis highlight the nature of the causative mutated genes[J]. J Dent Res, 2018, 97(12): 1306-1316.
14 Alappat S, Zhang ZY, Chen YP. Msx homeobox gene family and craniofacial development[J]. Cell Res, 2003, 13(6): 429-442.
15 Wang Y, Kong H, Mues G, et al. Msx1 mutations: how do they cause tooth agenesis[J]. J Dent Res, 2011, 90(3): 311-316.
16 Zhang XX, Wong SW, Han D, et al. Simultaneous occurence of an autosomal dominant inherited MSX1 mutation and an X-linked recessive inherited EDA mutation in one Chinese family with non-syndromic oligodontia[J]. Chin J Dent Res, 2015, 18(4): 229-234.
17 Liang J, von den Hoff J, Lange J, et al. MSX1 mutations and associated disease phenotypes: genotype-phenotype relations[J]. Eur J Hum Genet, 2016, 24(12): 1663-1670.
18 Matalova E, Fleischmannova J, Sharpe PT, et al. Tooth agenesis: from molecular genetics to molecular dentistry[J]. J Dent Res, 2008, 87(7): 617-623.
19 Yang Y, Zhu JX, Chiba YT, et al. Enamel defects of Axenfeld-Rieger syndrome and the role of PITX2 in its pathogenesis[J]. Oral Dis, 2023, 29(8): 3654-3664.
20 Tran TQ, Kioussi C. Pitx genes in development and disease[J]. Cell Mol Life Sci, 2021, 78(11): 4921-4938.
21 Arte S, Pöyhönen M, Myllymäki E, et al. Craniofacial and dental features of Axenfeld-Rieger syndrome patients with PITX2 mutations[J]. Orthod Craniofac Res, 2023, 26(3): 320-330.
22 Lan R, Wu YQ, Dai QG, et al. Gene mutations and chromosomal abnormalities in syndromes with tooth agenesis[J]. Oral Dis, 2023, 29(6): 2401-2408.
23 Sarkar T, Ranjan P, Kanathur S, et al. An in vitro and computational validation of a novel loss-of-functional mutation in PAX9 associated with non-syndromic tooth agenesis[J]. Mol Genet Genomics, 2023, 298(1): 183-199.
24 Feng XY, Wu XS, Wang JS, et al. Homeobox protein MSX-1 inhibits expression of bone morphogenetic protein 2, bone morphogenetic protein 4, and lymphoid enhancer-binding factor 1 via Wnt/ β-catenin signaling to prevent differentiation of dental mesenchymal cells during the late bell stage[J]. Eur J Oral Sci, 2018, 126(1): 1-12.
25 Zheng JL, Yu M, Liu HC, et al. Novel MSX1 va-riants identified in families with nonsyndromic oligodontia[J]. Int J Oral Sci, 2021, 13(1): 2.
26 Intarak N, Theerapanon T, Ittiwut C, et al. A novel PITX2 mutation in non-syndromic orodental anomalies[J]. Oral Dis, 2018, 24(4): 611-618.
27 张亲, 林师仪, 张婷婷, 等. PITX2突变导致非综合征型先天缺牙的遗传研究[J]. 口腔医学研究, 2022, 38(7): 628-631.
Zhang Q, Lin SY, Zhang TT, et al. Genetic study of PITX2 mutation leading to non-syndromic tooth agenesis[J]. J Oral Sci Res, 2022, 38(7): 628-631.
28 Zhang F, Zhang LS, He L, et al. A PITX2 splice-site mutation in a family with Axenfeld-Rieger syndrome leads to decreased expression of nuclear PITX2 protein[J]. Int Ophthalmol, 2021, 41(4): 1503-1511.
29 Fujimori S, Novak H, Weissenböck M, et al. Wnt/ β-catenin signaling in the dental mesenchyme regulates incisor development by regulating Bmp4[J]. Dev Biol, 2010, 348(1): 97-106.
30 Chen Y, Wang Z, Lin C, et al. Activated epithelial FGF8 signaling induces fused supernumerary incisors[J]. J Dent Res, 2022, 101(4): 458-464.
31 Narwidina A, Miyazaki A, Iwata K, et al. Iroquois homeobox 3 regulates odontoblast proliferation and differentiation mediated by Wnt5a expression[J]. Biochem Biophys Res Commun, 2023, 650: 47-54.
32 Sun RQ, Li SY, Xia B, et al. Detection of novel va-riant and functional study in a Chinese family with nonsyndromic oligodontia[J]. Oral Dis, 2023, 29(5): 2177-2187.
33 Nakatomi M, Wang XP, Key D, et al. Genetic inter-actions between Pax9 and Msx1 regulate lip develop-ment and several stages of tooth morphogenesis[J]. Dev Biol, 2010, 340(2): 438-449.
34 Intarak N, Tongchairati K, Termteerapornpimol K, et al. Tooth agenesis patterns and variants in PAX9: a systematic review[J]. Jpn Dent Sci Rev, 2023, 59: 129-137.
35 Punj A, Yih J, Rogoff GS. Interdisciplinary management of nonsyndromic tooth agenesis in the digital age[J]. J Am Dent Assoc, 2021, 152(4): 318-328.
36 Tavajohi-Kermani H, Kapur R, Sciote JJ. Tooth agenesis and craniofacial morphology in an ortho-dontic population[J]. Am J Orthod Dentofacial Orthop, 2002, 122(1): 39-47.
37 Tsai CY, Liao JB, Lee YC, et al. HOXC8 mediates osteopontin expression in gastric cancer cells[J]. J Cancer, 2023, 14(13): 2552-2561.
38 Zheng MM, Wu LF, Xiao RY, et al. Integrated analysis of coexpression and a tumor-specific ceRNA network revealed a potential prognostic biomarker in breast cancer[J]. Transl Cancer Res, 2023, 12(4): 949-964.
39 Picchi J, Trombi L, Spugnesi L, et al. HOX and TALE signatures specify human stromal stem cell populations from different sources[J]. J Cell Phy-siol, 2013, 228(4): 879-889.
40 Song WP, Jin LY, Zhu MD, et al. Clinical trials using dental stem cells: 2022 update[J]. World J Stem Cells, 2023, 15(3): 31-51.
41 Yang HQ, Fan J, Cao YY, et al. Distal-less homeobox 5 promotes the osteo-/dentinogenic differentiation potential of stem cells from apical papilla by activating histone demethylase KDM4B through a po-sitive feedback mechanism[J]. Exp Cell Res, 2019, 374(1): 221-230.
42 Viale-Bouroncle S, Klingelhöffer C, Ettl T, et al. A protein kinase A (PKA)/β-catenin pathway sustains the BMP2/DLX3-induced osteogenic differentiation in dental follicle cells (DFCs)[J]. Cell Signal, 2015, 27(3): 598-605.
43 Nagano R, Fujii S, Hasegawa K, et al. Wnt signa-ling promotes tooth germ development through YAP1-TGF‑β signaling[J]. Biochem Biophys Res Commun, 2022, 630: 64-70.
44 Qu BB, Liu OS, Fang XD, et al. Distal-less homeobox 2 promotes the osteogenic differentiation potential of stem cells from apical papilla[J]. Cell Tissue Res, 2014, 357(1): 133-143.
45 周勇, 朱明会, 黄旭瑶, 等. 探讨MSX1基因缺失导致的牙发育异常的机制及可能的信号通路[J]. 临床口腔医学杂志, 2021, 37(12): 716-719.
Zhou Y, Zhu MH, Huang XY, et al. To explore the mechanism and possible signal pathways of abnormal tooth development caused by MSX1 gene deletion[J]. J Clin Stomatol, 2021, 37(12): 716-719.
46 Wang X, Liu W, Wang PY, et al. RNA interference of long noncoding RNA HOTAIR suppresses autophagy and promotes apoptosis and sensitivity to cisplatin in oral squamous cell carcinoma[J]. J Oral Pathol Med, 2018, 47(10): 930-937.
47 Li BJ, Lv YJ, Zhang C, et al. lncRNA HOXA11-AS maintains the stemness of oral squamous cell carcinoma stem cells and reduces the radiosensitivity by targeting miR-518a-3p/PDK1[J]. J Oral Pathol Med, 2023, 52(3): 216-225.
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