黑色素瘤相关抗原D1在小鼠牙发育过程中的动态表达规律与调控作用研究

余侠; 袁洪燕; 李蒙; 张艺馨; 周勇全; 侯万邦; 温秀杰

doi:10.16016/j.2097-0927.202202045

您当前的位置：

首页 >

文章列表页 >

黑色素瘤相关抗原D1在小鼠牙发育过程中的动态表达规律与调控作用研究

基础医学 | 更新时间：2026-01-09

- 黑色素瘤相关抗原D1在小鼠牙发育过程中的动态表达规律与调控作用研究
- Dynamic expression and regulation of Mage-D1 during tooth development in mice
- 陆军军医大学学报 2022年44卷第14期页码：1431-1439
- 作者机构：
  
  1.646000 四川泸州，西南医科大学附属口腔医院正畸科
  2.401120 重庆，重庆医科大学附属口腔医院预防保健科
  3.030000 太原，中国人民解放军联勤保障部队第985医院口腔科
  4.400042 重庆，陆军特色医学中心口腔科
- 作者简介：
  
  [温秀杰，E-mail：wenxiujie@tom.comWEN Xiujie, E-mail: wenxiujie@tom.com
- 基金信息：
  
  国家自然科学基金面上项目(81970906);四川省科技计划项目(2019YJ0689)
- DOI：10.16016/j.2097-0927.202202045
  中图分类号： R322.41;R329.1;R394.2
- 收稿：2022-02-13，
  
  修回：2022-03-22，
  
  纸质出版：2022-07-30
- 稿件说明：
移动端阅览
余侠, 袁洪燕, 李蒙, 等. 黑色素瘤相关抗原D1在小鼠牙发育过程中的动态表达规律与调控作用研究[J]. 陆军军医大学学报, 2022,44(14):1431-1439.

Xia YU, Hongyan YUAN, Meng LI, et al. Dynamic expression and regulation of Mage-D1 during tooth development in mice[J]. Journal of Army Medical University, 2022, 44(14): 1431-1439.
余侠, 袁洪燕, 李蒙, 等. 黑色素瘤相关抗原D1在小鼠牙发育过程中的动态表达规律与调控作用研究[J]. 陆军军医大学学报, 2022,44(14):1431-1439. DOI： 10.16016/j.2097-0927.202202045.

Xia YU, Hongyan YUAN, Meng LI, et al. Dynamic expression and regulation of Mage-D1 during tooth development in mice[J]. Journal of Army Medical University, 2022, 44(14): 1431-1439. DOI： 10.16016/j.2097-0927.202202045.

摘要

目的

研究黑色素瘤相关抗原D1(mdanoma associated antigen D1

Mage-D1)在小鼠出生后不同牙发育阶段的动态表达规律，以及敲除Mage-D1在体内对小鼠牙发育造成的影响。

方法

C57-BL/6野生型乳鼠分为出生后1、4、7、11、15 d等5组(

=3)，HE染色观察出生后小鼠下颌第一磨牙的发育动态，免疫组织化学染色观察Mage-D1及同源盒基因Dlx1、Msx1在小鼠出生后牙发育不同阶段的表达情况。选择出生后1、3月龄的Mage-D1纯合敲除鼠(knockout type

KO)、野生小鼠(wild type

WT)进行表型观察(

=6)，并对下颌骨进行Micro-CT扫描，分析牙齿及下颌骨的相关数据。

结果

小鼠出生后第1天，下颌第一磨牙处于钟状晚期，无明显的硬组织形成；第4天，牙本质与牙釉质交替形成，牙冠开始发育；第7天，上皮根鞘形成，牙根开始发育；第11天，牙釉质及冠部牙本质发育基本完成，牙根约发育至一半；第15天，牙根进一步发育，达到2/3以上，牙骨质形成。从小鼠出生后1~15 d，Mage-D1及同源盒基因Dlx1、Msx1全程在成釉细胞及成牙本质细胞中呈阳性表达。与WT小鼠相比，KO小鼠体质量明显增加(

0.05)；牙齿在数目上与野生型小鼠一致，但外观上稍有差异，表现为切牙不易着色以及磨牙更易磨损。但牙及牙槽骨的密度未发现明显差异。

结论

Mage-D1与Dlx1、Msx1可能共同参与了小鼠牙釉质及牙本质的形成；Mage-D1基因敲除小鼠出现肥胖体征同时牙齿表型发生改变。

Abstract

Objective

To investigate the dynamic expression profile of mdanoma associated antigen D1 (Mage-D1) at different tooth development stages in mice after birth

and explore the effect of Mage-D1 knockout on tooth development

in vivo

Methods

C57-BL/6 wild-type suckling mice were grouped according to their age (1

11 and 15 d after birth

=3 in each group). Tissue samples were prepared and the developmental dynamics of the first mandibular molars in mice were observed by HE staining. Immunohistochemical staining was used to observe the expression of Mage-D1 as well as the homologous box genes Dlx1

and Msx1 at different stages of postnatal tooth development in mice. The Mage-D1 homozygous knockout mice (KO) and wild-type mice (WT) aged 1 and 3 months (

=6 in each group) were selected for phenotypic observation

and micro-CT scanning for mandible was performed to analyze the data of teeth and mandible.

Results

Morphological observation showed that on postnatal day 1

the first mandibular molar was in the late bell-shaped stage without obvious hard tissue formation; on day 4

dentin and enamel alternatively formed and crown began to develop; on day 7

epithelial root sheaths shaped and root development initiated; on day 11

the enamel and crown dentin were almost completed

with the root about half developed; on day 15

the root of the tooth further developed

reaching more than 2/3

and the cementum was formed. Mage-D1 and the homeobox genes Dlx1 and Msx1 were positively expressed in both ameloblasts and odontoblasts of mice throughout the period from 1 d to 15 d after birth. As compared with WT mice

the body weight of KO mice was increased (

0.05); though the number of teeth was the same in the 2 groups

the teeth appearance in KO group was slightly different

with incisors less stained and molars more easily worn. Scanning results indicated no significant difference in the density of teeth and alveolar bone.

Conclusion

Mage-D1

Dlx1 and Msx1 may contribute together to the formation of tooth enamel and dentin in mice

and the mice with Mage-D1 gene knockout present obesity signs and altered tooth phenotype.

关键词

Keywords

references

BRAGASON B T, PALSDOTTIR A. Interaction of PrP with NRAGE, a protein involved in neuronal apoptosis[J]. Mol Cell Neurosci, 2005, 29(2): 232-244. DOI: 10.1016/j.mcn.2005.02.013.

WILLIAMS M E, STRICKLAND P, WATANABE K, et al . UNC5H1 induces apoptosis via its juxtamembrane region through an interaction with NRAGE[J ] . J Biol Chem, 2003, 278(19): 17483-17490. DOI: 10.1074/jbc.M300415200.

YANG Q Y, OU C, LIU M, et al . NRAGE promotes cell proliferation by stabilizing PCNA in a ubiquitin-proteasome pathway in esophageal carcinomas[J ] . Carcinogenesis, 2014, 35(7): 1643-1651. DOI: 10.1093/carcin/bgu084.

余侠. Mage-D1的分子生物学特性及参与牙发育调控的研究进展[J]. 重庆医学, 2021, 50(5): 865-869. DOI: 10.3969/j.issn.1671-8348.2021.05.033.

YU X. Mage-D1 molecular biological characteristics and research progress in the regulation of tooth development[J]. Chongqing Med, 2021, 50(5): 865-869. DOI: 10.3969/j.issn.1671-8348.2021.05.033.

SASAKI A, MASUDA Y, IWAI K, et al . A RING finger protein Praja1 regulates Dlx5-dependent transcription through its ubiquitin ligase activity for the Dlx/Msx-interacting MAGE/Necdin family protein, Dlxin-1[J ] . J Biol Chem, 2002, 277(25): 22541-22546. DOI: 10.1074/jbc.M109728200.

DAVIDEAU J L, DEMRI P, HOTTON D, et al . Comparative study of MSX-2, DLX-5, and DLX-7 gene expression during early human tooth development[J ] . Pediatr Res, 1999, 46(6): 650. DOI: 10.1203/00006450-199912000-00015.

TAN Y F, TESTA J R. DLX genes: roles in development and cancer[J]. Cancers, 2021, 13(12): 3005. DOI: 10.3390/cancers13123005.

FENG X Y, WU X S, WANG J S, et al . Homeobox protein MSX-1 inhibits expression of bone morphogenetic protein 2, bone morphogenetic protein 4, and lymphoid enhance r-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. DOI: 10.1111/eos.12390.

王莹莹, 储庆, 杨琨, 等. p75NTR敲除对小鼠股骨矿化发育的抑制作用[J]. 第三军医大学学报, 2017, 39(12): 1245-1250. DOI: 10.16016/j.1000-5404.201702160.

WANG Y Y, CHU Q, YANG K, et al . Knocking out p75 neurotrophin receptor suppresses mineralization in the femurs of mice[J ] . J Third Mil Med Univ, 2017, 39(12): 1245-1250. DOI: 10.16016/j.1000-5404.201702160.

唐莹, 姜晓, 韩飞, 等. Sox30基因敲除致小鼠睾丸间质细胞增殖异常的研究[J]. 第三军医大学学报, 2021, 43(11): 1063-1073. DOI: 10.16016/j.1000-5404.202102044.

TANG Y, JIANG X, HAN F, et al . Abnormal proliferation of Leydig cells in Sox30 knockout mice[J ] . J Third Mil Med Univ, 2021, 43(11): 1063-1073. DOI: 10.16016/j.1000-5404.202102044.

刘洁, 沈梅, 张晶晶, 等. 牙齿发育及其干细胞分化的调控机制[J]. 四川医学, 2020, 41(6): 653-661. DOI: 10.16252/j.cnki.issn1004-0501-2020.06.021.

LIU J, SHEN M, ZHANG J J, et al . Regulatory mechanisms of tooth development and stem cell differentiation[J ] . Sichuan Med J, 2020, 41(6): 653-661. DOI: 10.16252/j.cnki.issn1004-0501-2020.06.021.

陈茜, 范志朋, 张琛. 组蛋白去甲基化酶KDM2B在小鼠磨牙及颌骨发育中的时空表达[J]. 北京口腔医学, 2018, 26(5): 241-245.

CHEN Q, FAN Z P, ZHANG C. Spatial and temporal expression of histone demethylase KDM2B in the development of molar and mandible in mice[J]. Beijing J Stomatol, 2018, 26(5): 241-245.

陈栋, 李晓聪, 鲁方丽, 等. 液泡分选蛋白4B在小鼠牙胚发育的时空表达[J]. 实用口腔医学杂志, 2018, 34(4): 442-445. DOI: 10.3969/j.issn.1001-3733.2018.04.002.

CHEN D, LI X C, LU F L, et al . The spatio-temporal expression of VPS4 B during molar tooth germ development in mice[J ] . J Pract Stomatol, 2018, 34(4): 442-445. DOI: 10.3969/j.issn.1001-3733.2018.04.002.

杜文, 罗天, 于海洋. 机械应力相关调控蛋白在小鼠磨牙发育中的时空表达[J]. 四川大学学报(医学版), 2021, 52(1): 82-86. DOI: 10.12182/20210160105.

DU W, LUO T, YU H Y. The spatiotemporal expression patterns of mechanical-stress related regulatory proteins in mouse molar development[J]. J Sichuan Univ Med Sci Ed, 2021, 52(1): 82-86. DOI: 10.12182/20210160105.

POLD M, ZHOU J, CHEN G L, et al . Identification of a new, unorthodox member of the MAGE gene family[J ] . Genomics, 1999, 59(2): 161-167. DOI: 10.1006/geno.1999.5870.

TEUBER J, MUELLER B, FUKABORI R, et al . The ubiquitin ligase Praja1 reduces NRAGE expression and inhibits neuronal differentiation of PC12 cells[J ] . PLoS One, 2013, 8(5): e63067. DOI: 10.1371/journal.pone.0063067.

ZHANG G, ZHOU H D, XUE X Y. Complex roles of NRAGE on tumor[J]. Tumour Biol, 2016, 37(9): 11535-11540. DOI: 10.1007/s13277-016-5084-0.

JIANG X D, JIANG X F, YANG Z. NRAGE confers poor prognosis and promotes proliferation, invasion, and chemoresistance in gastric cancer[J]. Gene, 2018, 668: 114-120. DOI: 10.1016/j.gene.2018.05.060.

SHIMIZU D, KANDA M, SUGIMOTO H, et al . NRAGE promotes the malignant phenotype of hepatocellular carcinoma[J ] . Oncol Lett, 2016, 11(3): 1847-1854. DOI: 10.3892/ol.2016.4120.

QI S, WU Q, MA J, et al . Effects of neurotrophin receptor-mediated MAGE homology on proliferation and odontoblastic differentiation of mouse dental pulp cells[J ] . Cell Prolif, 2015, 48(2): 221-230. DOI: 10.1111/cpr.12171.

WU Q, QI S C, MA J, et al . The effect of NRAGE on cell cycle and apoptosis of human dental pulp cells and MDPC-23[J ] . Int J Clin Exp Med, 2015, 8(7): 10657-10667.

WU Q, LI J, SONG P P, et al . Knockdown of NRAGE induces odontogenic differentiation by activating NF-κB signaling in mouse odontoblast-like cells[J ] . Connect Tissue Res, 2019, 60(2): 71-84. DOI: 10.1080/03008207.2018.1439484.

LIU H X, ZHANG X, YANG Q X, et al . Knockout of NRAGE promotes autophagy-related gene expression and the periodontitis process in mice[J ] . Oral Dis, 2021, 27(3): 589-599. DOI: 10.1111/odi.13575.

杨琨, 李骏, 丰奇昊, 等. MAGE-D1对大鼠牙胚来源外胚间充质干细胞增殖迁移能力的影响[J]. 遵义医学院学报, 2018, 41(5): 569-575. DOI: 10.14169/j.cnki.zunyixuebao.2018.0115.

YANG K, LI J, FENG Q H, et al . The effects of MAGE-D1 on proliferation and migration of ectomesenchymal stem cells originated from rat teeth germ[J ] . J Zunyi Med Univ, 2018, 41(5): 569-575. DOI: 10.14169/j.cnki.zunyixuebao.2018.0115.

YANG K, WANG Y Y, JU Y X, et al . p75 neurotrophin receptor regulates differential mineralization of rat ectomesenchymal stem cells[J ] . Cell Prolif, 2017. DOI: 10.1111/cpr.12290.

罗玉婷, 杨正艳, 李蒙, 等. Mage-D1与活化后的p75神经营养因子受体结合可正向调节大鼠外胚间充质干细胞的矿化[J]. 南方医科大学学报, 2021, 41(10): 1547-1553. DOI: 10.12122/j.issn.1673-4254.2021.10.14.

LUO Y T, YANG Z Y, LI M, et al . Mage-D1 binding to activated p75NTR positively regulates mineralization of rat ectomesenchymal stem cells in vitro [J ] . J South Med Univ, 2021, 41(10): 1547-1553. DOI: 10.12122/j.issn.1673-4254.2021.10.14..

ZHAO M Z, WANG Y Y, LI G, et al . The role and potential mechanism of p75NTR in mineralization via in vivo p75NTR knockout mice and in vitro ectomesenchymal stem cells[J ] . Cell Prolif, 2020, 53(2): e12758. DOI: 10.1111/cpr.12758..

MOURI A, SASAKI A, WATANABE K, et al . MAGE-D1 knockout mice express depressive endophenotypes associated with downrgulation of serotonin transporter ubiquitylation[J ] . J Pharmacological Sci, 2012, 118: 99P-99P. DOI: 10.1523/JNEUROSCI.6458-11.2012.

LIU M, XU L J, MA X, et al . MAGED1 is a negative regulator of bone remodeling in mice[J ] . Am J Pathol, 2015, 185(10): 2653-2667. DOI: 10.1016/j.ajpath.2015.06.017.

DE BACKER J F, MONLEZUN S, DETRAUX B, et al . Deletion of Maged1 in mice abolishes locomotor and reinforcing effects of cocaine[J ] . EMBO Rep, 2018, 19(9): 1-17. DOI: 10.15252/embr.201745089.

WANG Q H, TANG J, JIANG S J, et al . Inhibition of PPARγ, adipogenesis and insulin sensitivity by MAGED1[J ] . J Endocrinol, 2018, 239(2): 167-180. DOI: 10.1530/JOE-18-0349.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

iRoot SP用于根管三维充填的封闭性研究

Mage-D1对敲除小鼠骨髓间充质干细胞的矿化调控作用