Li Mingyue, Zhang Jie, Xiao Shuang, Liu Xinyang, Song Shuai, Ye Xiaoyuan, Bi Ruonan, Gao Yuguang, Zhang Li
School of Medicine, Qingdao Huanghai University, Qingdao, Shandong, China.
School of Stomatology, Binzhou Medical University, Yantai, Shandong, China.
PLoS One. 2025 Jul 18;20(7):e0328263. doi: 10.1371/journal.pone.0328263. eCollection 2025.
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.
隐性低矿化型釉质发育不全与牙胚相关磷蛋白（ODAPH）的突变有关。与人类表型一致，Odaph基因敲除小鼠表现出釉质矿化缺陷，成釉细胞从釉质表面脱离。为了阐明其机制基础，我们使用成釉细胞系细胞（ALCs）研究了ODAPH在成釉细胞黏附和矿化中的作用。主要研究结果表明，Odaph过表达增强了层粘连蛋白γ2（LAMC2）/整合素β6（ITGB6）/转化生长因子-β1（TGF-β1）/碱性磷酸酶（ALP）信号通路的活性。值得注意的是，免疫共沉淀证实了ODAPH与LAMC2之间的相互作用。功能分析表明，ITGB6激活TGF-β1/ALP信号级联反应。整合素抑制剂（CWHM-12）可消除ODAPH介导的TGF-β1/ALP诱导。TGF-β1正向调节LAMC2/ITGB6的表达和ALP活性。这些结果表明，ODAPH通过LAMC2/ITGB6/TGF-β1/ALP信号轴协调成釉细胞的黏附和矿化。
