Ablation of Fam20c causes amelogenesis imperfecta via inhibiting Smad dependent BMP signaling pathway

Biology Direct

Jing Liu¹  Limin Mao¹  Wuliji Saiyin¹  Lili Li²  Xiaohua Xie³ 

[1] Department of Stomatology, the 1st Affiliated Hospital of Harbin Medical University, 23 Youzheng Road, Nangang, 150001, Harbin, Heilongjiang, China;Department of Stomatology, the 1st Affiliated Hospital of Harbin Medical University, 23 Youzheng Road, Nangang, 150001, Harbin, Heilongjiang, China;Longjiang scholar laboratory, the 1st Affiliated Hospital of Harbin Medical University, 23 Youzheng Road, Nangang, 150001, Harbin, Heilongjiang, China;Institute of Hard Tissue Development and Regeneration, the 2nd Affiliated Hospital of Harbin Medical University, 150086, Harbin, Heilongjiang, China;

关键词: FAM20C;    Amelogenesis Imperfecta;    BMP signaling pathway;    Ameloblast differentiation;   

DOI  :  10.1186/s13062-020-00270-7

来源: Springer

【 摘 要 】

BackgroundAmelogenesis 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.ResultsIn 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.Conclusionthe 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.

【 授权许可】

CC BY