Department of Stomatology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China.
Department of Pediatrics and Preventive Dentistry, Hospital Affiliated to Binzhou Medical University, Binzhou, Shandong, China.
Dev Dyn. 2021 Oct;250(10):1505-1517. doi: 10.1002/dvdy.336. Epub 2021 Mar 31.
Mutation in Odontogenesis-associated phosphoprotein (ODAPH) has been reported to cause recessive hypomineralized amelogenesis imperfecta (AI) in human. However, the exact role of ODAPH in amelogenesis is still unknown.
ODAPH was identified as a novel constituent of the atypical basal lamina located at the interface between maturation ameloblasts and the enamel by dual immunofluorescence staining of ODAPH and LAMC2. Odaph knockout mice were generated to explore the function of ODAPH in amelogenesis. Odaph mice teeth showed severely attrition and reduced enamel mineralization. Histological analysis showed from transition or early-maturation stage, ameloblasts were rapidly shortened, lost cell polarity, and exhibited cell pathology. Abundant enamel matrix marked by amelogenin was retained. Temporary cyst-like structures were formed between flattened epithelial cells and the enamel from maturation stage to eruption. The integrity of the atypical basal lamina was impaired indicated by the reduced diffuse expression of LAMC2 and AMTN. The expression of maturation stage related genes of Amtn, Klk4, Integrinβ6 and Slc24a4 were significantly decreased.
Our results suggested Odaph played vital roles during amelogenesis by maintaining the integrity of the atypical basal lamina in maturation stage, which may contribute to a better understanding of the pathophysiology of human AI.
Odontogenesis-associated phosphoprotein（ODAPH）的突变已被报道可导致人类隐性低矿化型牙釉质不全（AI）。然而，ODAPH 在釉质形成中的确切作用仍不清楚。
通过 ODAPH 和 LAMC2 的双重免疫荧光染色，ODAPH 被鉴定为位于成熟成釉细胞和釉质界面的非典型基底层的一种新成分。通过 Odaph 基因敲除小鼠来探索 ODAPH 在釉质形成中的功能。Odaph 小鼠的牙齿出现严重磨损和釉质矿化减少。组织学分析表明，从过渡或早期成熟阶段开始，成釉细胞迅速缩短，失去细胞极性，并表现出细胞病理学。大量由釉原蛋白标记的釉质基质被保留下来。在从成熟阶段到萌出阶段，扁平上皮细胞和釉质之间形成了临时的类似囊肿的结构。非典型基底层的完整性受损，LAMC2 和 AMTN 的弥散表达减少。Amtn、Klk4、Integrinβ6 和 Slc24a4 的成熟阶段相关基因的表达显著降低。
我们的结果表明，Odaph 通过维持成熟阶段非典型基底层的完整性，在釉质形成中发挥着重要作用，这可能有助于更好地理解人类 AI 的病理生理学。
