von Willebrand factor D and EGF domains regulate ameloblast differentiation and enamel formation

被引：8

作者：

Iwata, Kokoro ^{[1
]}

Kawarabayashi, Keita ^{[2
]}

Yoshizaki, Keigo ^{[3
]}

Tian, Tian ^{[3
]}

Saito, Kan ^{[4
]}

Sugimoto, Asuna ^{[1
]}

Kurogoushi, Rika ^{[1
]}

Yamada, Aya ^{[4
]}

Yamamoto, Akihito ^{[5
]}

Kudo, Yasuei ^{[6
]}

Ishimaru, Naozumi ^{[7
]}

Fukumoto, Satoshi ^{[4
,8
]}

Iwamoto, Tsutomu ^{[1
]}

机构：

[1] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Pediat Dent Special Needs Dent, Div Oral Hlth Sci, Tokyo 1138549, Japan

[2] Tokushima Univ, Inst Biomed Sci, Dept Pediat Dent, Grad Sch, Tokushima, Japan

[3] Kyushu Univ, Div Oral Hlth Growth & Dev, Orthodont & Dentofacial Orthoped Sect, Fac Dent Sci, Fukuoka, Japan

[4] Tohoku Univ, Dept Oral Hlth & Dev Sci, Pediat Dent Div, Grad Sch Dent, Sendai, Miyagi, Japan

[5] Tokushima Univ, Inst Biomed Sci, Dept Tissue Regenerat, Grad Sch, Tokushima, Japan

[6] Tokushima Univ, Inst Biomed Sci, Dept Oral Biosci, Grad Sch, Tokushima, Japan

[7] Tokushima Univ, Inst Biomed Sci, Dept Oral Mol Pathol, Grad Sch, Tokushima, Japan

[8] Kyushu Univ, Div Oral Hlth Growth & Dev, Pediat Dent Sect, Fac Dent Sci, Fukuoka, Japan

来源：

JOURNAL OF CELLULAR PHYSIOLOGY | 2022年 / 237卷 / 03期

关键词：

ameloblast differentiation; enamel formation; extracellular matrix protein; inner dental epithelium; N-cadherin; Vwde; CELL-CELL ADHESION; DENTAL EPITHELIUM; TOOTH DEVELOPMENT; EXPRESSION; CADHERIN; MATRIX; MORPHOGENESIS; LOCALIZATION; MOLECULES; GROWTH;

D O I：

10.1002/jcp.30667

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Cell- and tissue-specific extracellular matrix (ECM) composition plays an important role in organ development, including teeth, by regulating cell behaviors, such as cell proliferation and differentiation. Here, we demonstrate for the first time that von Willebrand factor D and epidermal growth factor (EGF) domains (Vwde), a previously uncharacterized ECM protein, is specifically expressed in teeth and regulates cell proliferation and differentiation in inner enamel epithelial cells (IEEs) and enamel formation. We identified the Vwde as a novel ECM protein through bioinformatics using the NCBI expressed sequence tag database for mice. Vwde complementary DNA encodes 1773 amino acids containing a signal peptide, a von Willebrand factor type D domain, and tandem calcium-binding EGF-like domains. Real-time polymerase chain reaction demonstrated that Vwde is highly expressed in tooth tissue but not in other tissues including the brain, lung, heart, liver, kidney, and bone. In situ hybridization revealed that the IEEs expressed Vwde messenger RNA in developing teeth. Immunostaining showed that VWDE was localized at the proximal and the distal ends of the pericellular regions of the IEEs. Vwde was induced during the differentiation of mouse dental epithelium-derived M3H1 cells. Vwde-transfected M3H1 cells secreted VWDE protein into the culture medium and inhibited cell proliferation, whereas ameloblastic differentiation was promoted. Furthermore, Vwde increased the phosphorylation of extracellular signal-regulated kinase 1/2 and protein kinase B and strongly induced the expression of the intercellular junction protein, N-cadherin (Ncad). Interestingly, the suppression of endogenous Vwde inhibited the expression of Ncad. Finally, we created Vwde-knockout mice using the CRISPR-Cas9 system. Vwde-null mice showed low mineral density, rough surface, and cracks in the enamel, indicating the enamel hypoplasia phenotype. Our findings suggest that Vwde assembling the matrix underneath the IEEs is essential for Ncad expression and enamel formation.

引用

页码：1964 / 1979

页数：16

共 37 条

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