Ablation of Runx2 in Ameloblasts Suppresses Enamel Maturation in Tooth Development. 2018

Qing Chu, and Yan Gao, and Xianhua Gao, and Zhiheng Dong, and Wenying Song, and Zhenzhen Xu, and Lili Xiang, and Yumin Wang, and Li Zhang, and Mingyu Li, and Yuguang Gao
Department of Pediatrics and Preventive Dentistry, Hospital Affiliated to Binzhou Medical University, Binzhou, 256600, Shandong, China.

Runt-related transcription factor 2 (Runx2) is involved in the early stage of tooth development. However, only few studies have reported the role of Runx2 in enamel development, which may be attributed to that Runx2 full knockout mice cannot survive after birth. In the present study, we successfully established a Runx2-deficient mouse model using a conditional knockout (cKO) method. We observed a significant reduction in the degree of mineralization and the decreased size of enamel rods in cKO mice. Histological analysis showed the retained enamel proteins in enamel layer at maturation stage in cKO molars. Further analysis by qRT-PCR revealed that the expressions of genes encoding enamel structure proteins, such as amelogenin (AMELX), ameloblastin (AMBN) and enamelin (ENAM), were increased in cKO enamel organs. On the other hand, the expression of kallikrein-related peptidase-4 (KLK4) at the mRNA and protein levels was dramatically decreased from late secretory stage to maturation stage in cKO enamel organs, while the expression of matrix metalloproteinase-20 (MMP-20) was not significantly altered. Finally, immunohistochemistry indicated that the uptake of amelogenins by ameloblasts was significantly decreased in cKO mice. Taken together, Runx2 played critical roles in controlling enamel maturation by increasing synthesis of KLK4 and decreasing synthesis of AMELX, AMBN and ENAM.

UI MeSH Term Description Entries
D007610 Kallikreins Proteolytic enzymes from the serine endopeptidase family found in normal blood and urine. Specifically, Kallikreins are potent vasodilators and hypotensives and increase vascular permeability and affect smooth muscle. They act as infertility agents in men. Three forms are recognized, PLASMA KALLIKREIN (EC 3.4.21.34), TISSUE KALLIKREIN (EC 3.4.21.35), and PROSTATE-SPECIFIC ANTIGEN (EC 3.4.21.77). Kallikrein,Kininogenase,Callicrein,Dilminal,Kallidinogenase,Kalliginogenase,Kallikrein A,Kallikrein B',Kallikrein Light Chain,Kinin-Forming Enzyme,Padutin,alpha-Kallikrein,beta-Kallikrein,beta-Kallikrein B,Enzyme, Kinin-Forming,Kinin Forming Enzyme,Light Chain, Kallikrein,alpha Kallikrein,beta Kallikrein,beta Kallikrein B
D008903 Minerals Native, inorganic or fossilized organic substances having a definite chemical composition and formed by inorganic reactions. They may occur as individual crystals or may be disseminated in some other mineral or rock. (Grant & Hackh's Chemical Dictionary, 5th ed; McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Mineral
D003743 Dental Enamel A hard thin translucent layer of calcified substance which envelops and protects the dentin of the crown of the tooth. It is the hardest substance in the body and is almost entirely composed of calcium salts. Under the microscope, it is composed of thin rods (enamel prisms) held together by cementing substance, and surrounded by an enamel sheath. (From Jablonski, Dictionary of Dentistry, 1992, p286) Enamel,Enamel Cuticle,Dental Enamels,Enamel, Dental,Enamels, Dental,Cuticle, Enamel,Cuticles, Enamel,Enamel Cuticles,Enamels
D003746 Dental Enamel Proteins The proteins that are part of the dental enamel matrix. Enamel Proteins, Dental,Proteins, Dental Enamel
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D000565 Ameloblasts Cylindrical epithelial cells in the innermost layer of the ENAMEL ORGAN. Their functions include contribution to the development of the dentinoenamel junction by the deposition of a layer of the matrix, thus producing the foundation for the prisms (the structural units of the DENTAL ENAMEL), and production of the matrix for the enamel prisms and interprismatic substance. (From Jablonski's Dictionary of Dentistry, 1992) Ameloblast
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D050659 Core Binding Factor Alpha 1 Subunit A transcription factor that dimerizes with CORE BINDING FACTOR BETA SUBUNIT to form core binding factor. It contains a highly conserved DNA-binding domain known as the runt domain and is involved in genetic regulation of skeletal development and CELL DIFFERENTIATION. AML3 Transcription Factor,Acute Myeloid Leukemia 3 Protein,CBFA-1 Protein,CBFA1 Protein,CBFalpha Runt Domain Transcription Factor 1,CBFalpha1 Protein,Osf2 Transcription Factor,PEBP2alphaA Protein,Runx2 Protein,SEF1 Protein,SL3-3 Enhancer Factor 1,CBFA 1 Protein,SL3 3 Enhancer Factor 1
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D053523 Amelogenin A major dental enamel-forming protein found in mammals. In humans the protein is encoded by GENES found on both the X CHROMOSOME and the Y CHROMOSOME. Amelogenins

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