title: Abrogation of epithelial BMP2 and BMP4 causes Amelogenesis Imperfecta by reducing MMP20 and KLK4 expression.
abstract: 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.
authors.affiliation: Department of Stomatology, and Institute of Hard Tissue Development and Regeneration, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.|Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas, 75246, USA.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas, 75246, USA.|Department of Oral Biology, College of Stomatology, Dalian Medical University, Dalian, 116044, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas, 75246, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas, 75246, USA.
authors.forename: Priyam H
authors.initials: PH
authors.lastname: Jani
authors.affiliation: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas, 75246, USA.
authors.forename: Yongbo
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas, 75246, USA.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Stomatology, and Institute of Hard Tissue Development and Regeneration, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.|Heilongjiang Academy of Medical Sciences, Harbin, 150001, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, Texas, 75246, USA.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Qin
mesh_terms: D000567:Amelogenesis Imperfecta / Q000000981:diagnostic imaging* / Q000235:genetics; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics*; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics*; D004195:Disease Models, Animal; D015536:Down-Regulation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D017353:Gene Deletion; D055786:Gene Knockout Techniques; D006801:Humans; D007610:Kallikreins / Q000235:genetics* / Q000378:metabolism; D053519:Matrix Metalloproteinase 20 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018625:Microscopy, Atomic Force; D011859:Radiography; D015398:Signal Transduction
chemical_list: C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D007610:Kallikreins; C120801:kallikrein 4; D053519:Matrix Metalloproteinase 20; C507113:Mmp20 protein, mouse