Abrogation of epithelial BMP2 and BMP4 causes Amelogenesis Imperfecta by reducing MMP20 and KLK4 expression

• Published in: Scientific reports 2016-05, Vol.6 (1), p.25364-25364, Article 25364
• Main Authors: Xie, Xiaohua, Liu, Chao, Zhang, Hua, Jani, Priyam H., Lu, Yongbo, Wang, Xiaofang, Zhang, Bin, Qin, Chunlin
• Format: Article
• Language: English
• Subjects: 38; 631/136; 631/208/199; 82; 82/51; 82/80; AMBN protein; Ameloblasts; Amelogenesis imperfecta; Amelogenesis Imperfecta - diagnostic imaging; Amelogenesis Imperfecta - genetics; Animals; Bone morphogenetic protein 2; Bone Morphogenetic Protein 2 - genetics; Bone morphogenetic protein 4; Bone Morphogenetic Protein 4 - genetics; Dental enamel; Disease Models, Animal; Down-Regulation; Electron microscopy; Enamel; Epithelial Cells - cytology; Epithelial Cells - metabolism; Epithelium; Gene Deletion; Gene Knockout Techniques; Humanities and Social Sciences; Humans; Kallikreins - genetics; Kallikreins - metabolism; Matrix metalloproteinase; Matrix Metalloproteinase 20 - genetics; Matrix Metalloproteinase 20 - metabolism; Mice; Microscopy, Atomic Force; multidisciplinary; Proteins; Radiography; Scanning electron microscopy; Science; Secretion; Signal Transduction; Smad4 protein
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep25364

Amelogenesis Imperfecta (AI) can be caused by the deficiencies of enamel matrix proteins, molecules responsible for the transportation and secretion of enamel matrix components and proteases processing enamel matrix proteins. In the present study, we discovered the double deletion of bone morphogenetic protein 2 ( Bmp2 ) and bone morphogenetic protein 4 ( Bmp4 ) in the dental epithelium by K14-cre resulted in hypoplastic enamel and reduced density in X-ray radiography as well as shortened enamel rods under scanning electron microscopy. Such enamel phenotype was consistent with the diagnosis of hypoplastic amelogenesis imperfecta. Histological and molecular analyses revealed that the removal of matrix proteins in the mutant enamel was drastically delayed, which was coincided with the greatly reduced expression of matrix metalloproteinase 20 (MMP20) and kallikrein 4 (KLK4). Although the expression of multiple enamel matrix proteins was down-regulated in the mutant ameloblasts, the cleavage of ameloblastin was drastically impaired. Therefore, we attributed the AI primarily to the reduction of MMP20 and KLK4. Further investigation found that BMP/Smad4 signaling pathway was down-regulated in the K14-cre;Bmp2 f / f ;Bmp4 f / f ameloblasts, suggesting that the reduced MMP20 and KLK4 expression may be due to the attenuated epithelial BMP/Smad4 signaling.