Ablation of Fam20c causes amelogenesis imperfecta via inhibiting Smad dependent BMP signaling pathway
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...
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| Format: | Article |
| Language: | English |
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BMC
2020-10-01
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| Series: | Biology Direct |
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| Online Access: | http://link.springer.com/article/10.1186/s13062-020-00270-7 |
| _version_ | 1819228115419791360 |
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| author | Jing Liu Wuliji Saiyin Xiaohua Xie Limin Mao Lili Li |
| author_facet | Jing Liu Wuliji Saiyin Xiaohua Xie Limin Mao Lili Li |
| author_sort | Jing Liu |
| collection | DOAJ |
| description | 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;Fam20C fl/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. |
| first_indexed | 2024-12-23T10:52:09Z |
| format | Article |
| id | doaj.art-5d9cd76bf5c84fec8cd8206e21dc7825 |
| institution | Directory Open Access Journal |
| issn | 1745-6150 |
| language | English |
| last_indexed | 2024-12-23T10:52:09Z |
| publishDate | 2020-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Biology Direct |
| spelling | doaj.art-5d9cd76bf5c84fec8cd8206e21dc78252022-12-21T17:49:52ZengBMCBiology Direct1745-61502020-10-011511910.1186/s13062-020-00270-7Ablation of Fam20c causes amelogenesis imperfecta via inhibiting Smad dependent BMP signaling pathwayJing Liu0Wuliji Saiyin1Xiaohua Xie2Limin Mao3Lili Li4Department of Stomatology, the 1st Affiliated Hospital of Harbin Medical UniversityDepartment of Stomatology, the 1st Affiliated Hospital of Harbin Medical UniversityInstitute of Hard Tissue Development and Regeneration, the 2nd Affiliated Hospital of Harbin Medical UniversityDepartment of Stomatology, the 1st Affiliated Hospital of Harbin Medical UniversityDepartment of Stomatology, the 1st Affiliated Hospital of Harbin Medical UniversityAbstract 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;Fam20C fl/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.http://link.springer.com/article/10.1186/s13062-020-00270-7FAM20CAmelogenesis ImperfectaBMP signaling pathwayAmeloblast differentiation |
| spellingShingle | Jing Liu Wuliji Saiyin Xiaohua Xie Limin Mao Lili Li Ablation of Fam20c causes amelogenesis imperfecta via inhibiting Smad dependent BMP signaling pathway Biology Direct FAM20C Amelogenesis Imperfecta BMP signaling pathway Ameloblast differentiation |
| title | Ablation of Fam20c causes amelogenesis imperfecta via inhibiting Smad dependent BMP signaling pathway |
| title_full | Ablation of Fam20c causes amelogenesis imperfecta via inhibiting Smad dependent BMP signaling pathway |
| title_fullStr | Ablation of Fam20c causes amelogenesis imperfecta via inhibiting Smad dependent BMP signaling pathway |
| title_full_unstemmed | Ablation of Fam20c causes amelogenesis imperfecta via inhibiting Smad dependent BMP signaling pathway |
| title_short | Ablation of Fam20c causes amelogenesis imperfecta via inhibiting Smad dependent BMP signaling pathway |
| title_sort | ablation of fam20c causes amelogenesis imperfecta via inhibiting smad dependent bmp signaling pathway |
| topic | FAM20C Amelogenesis Imperfecta BMP signaling pathway Ameloblast differentiation |
| url | http://link.springer.com/article/10.1186/s13062-020-00270-7 |
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