Ablation of Fam20c causes amelogenesis imperfecta via inhibiting Smad dependent BMP signaling pathway
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RESEARCH
Open Access
Ablation of Fam20c causes amelogenesis imperfecta via inhibiting Smad dependent BMP signaling pathway Jing Liu1†, Wuliji Saiyin1†, Xiaohua Xie2, Limin Mao1* and Lili Li1,3*
Abstract Background: Amelogenesis imperfecta (AI) is a type of hereditary diseases that manifest defects in the formation or mineralization of enamel. Recently, it is reported that inactivation of FAM20C, a well-known Golgi casein kinase, caused AI. However, the mechanism of it is still unknown. The aim of this study was to explore the molecular mechanism of AI, which caused by ablation of FAM20C. Results: In the Sox2-Cre;Fam20Cfl/fl (cKO) mouse, we found abnormal differentiation of ameloblasts, improper formation and mineralization of enamel, and downregulation of both mRNA and protein level of enamel matrix proteins, including amelogenin (AMEL), ameloblastin (AMBN) and enamelin (ENAM). The levels of BMP2, BMP4 and BMP7, the ligands of BMP signaling pathway, and phosphorylation of Smad1/5/8, the key regulators of BMP signaling pathway, were all decreased in the enamel matrix and the ameloblast of the cKO mice, respectively. The expression of cyclin-dependent kinase inhibitor (P21), muscle segment homeobox genes 2 (Msx2), which are the target genes of the BMP signaling pathway, and laminin 3, the downstream factor of Msx2, were all significantly decreased in the ameloblasts of the cKO mice compared to the control mice. Conclusion: the results of our study suggest that ablation of FAM20C leads to AI through inhibiting the Smad dependent BMP signaling pathway in the process of amelogenesis. Keywords: FAM20C, Amelogenesis Imperfecta, BMP signaling pathway, Ameloblast differentiation
Background Amelogenesis imperfecta (AI) is a type of hereditary diseases that manifest defects in the formation or mineralization of enamel [1]. AI exhibit abnormally thin, soft, fragile, pitted and discolored enamel phenotype. Patients with AI often have some problems such as early tooth loss, eating difficulties, and pain. Therefore, understanding the biological mechanism of AI is essential for providing effective and potential clinical treatment for AI. * Correspondence: [email protected]; [email protected] † Jing Liu and Wuliji Saiyin contributed equally to this work. 1 Department of Stomatology, the 1st Affiliated Hospital of Harbin Medical University, 23 Youzheng Road, Nangang, Harbin 150001, Heilongjiang, China Full list of author information is available at the end of the article
There are many reasons for AI. During the secretory stage, ameloblasts secreted abundant enamel matrix proteins (EMPs), such as amelogenin (AMEL), ameloblastin (AMBN) and enamelin (ENAM), and numerous cell adhesion molecules and it is reported that mutations of these EMPs will cause Hypoplastic AI in human [2–7]. Hypomineralized AI is caused by maturation stage failure, giving rise to enamel that is of full thickness but is weak and fails prematurely [8]. During maturation stage, ameloblasts secrete two kinds of matrix proteases which are Matrix metallopeptidases
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