Odontogenesis-associated phosphoprotein (ODAPH) Promotes Ameloblast adhesion and alkaline phosphatase (ALP) expression via LAMC2/ ITGB6/TGF-β1 signaling pathway.

IF 2.6 3区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

PLoS ONE Pub Date : 2025-07-18 eCollection Date: 2025-01-01 DOI:10.1371/journal.pone.0328263

Mingyue Li, Jie Zhang, Shuang Xiao, Xinyang Liu, Shuai Song, Xiaoyuan Ye, Ruonan Bi, Yuguang Gao, Li Zhang

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Abstract

Recessive hypomineralized amelogenesis imperfecta has been linked to mutations in Odontogenesis-Associated Phosphoprotein (ODAPH). Consistent with human phenotypes, Odaph-null mice exhibit defective enamel mineralization with ameloblast detachment from the enamel surface. To elucidate the mechanistic basis, we investigated ODAPH's role in ameloblast adhesion and mineralization using ameloblast-lineage cells (ALCs). Key findings demonstrate that Odaph overexpression enhanced Lamininγ2 (LAMC2)/Integrinβ6(ITGB6)/TGF-β1/Alkaline Phosphatase(ALP) pathway activity. Notably, co-immunoprecipitation confirmed interactions between ODAPH and LAMC2. Functional analyses revealed that ITGB6 activates the TGF-β1/ALP signaling cascade. Inhibition of integrin (CWHM-12) abrogates ODAPH-mediated TGF-β1/ALP induction. TGF-β1 positively regulates both LAMC2/ITGB6 expression and ALP activity. These results establish that ODAPH orchestrates ameloblast adhesion and mineralization via the LAMC2/ITGB6/TGF-β1/ALP signaling axis.

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牙髓生成相关磷酸化蛋白（ODAPH）通过LAMC2/ ITGB6/TGF-β1信号通路促进成釉细胞粘附和碱性磷酸酶（ALP）的表达。

隐性低矿化成牙不全与牙形成相关磷酸蛋白（odoaph）突变有关。与人类表型一致，Odaph-null小鼠表现出牙釉质矿化缺陷，成釉细胞从牙釉质表面脱离。为了阐明其机制基础，我们利用成釉细胞系细胞（ALCs）研究了odoaph在成釉细胞粘附和矿化中的作用。主要研究结果表明，ograph过表达增强了LAMC2 /整合素β6 /TGF-β1/碱性磷酸酶（ALP）通路活性。值得注意的是，共免疫沉淀证实了oaph和LAMC2之间的相互作用。功能分析显示ITGB6激活TGF-β1/ALP信号级联。抑制整合素（CWHM-12）可消除odap介导的TGF-β1/ALP诱导。TGF-β1正调控LAMC2/ITGB6表达和ALP活性。这些结果表明odac通过LAMC2/ITGB6/TGF-β1/ALP信号轴调控成釉细胞粘附和矿化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

PLoS ONE 生物-生物学

CiteScore

6.20

自引率

5.40%

发文量

14242

审稿时长

3.7 months

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