Hepatocyte growth factor is involved in the morphogenesis of tooth germ in murine molars

Abstract

The patterns of gene expression for hepatocyte growth factor (HGF) and its receptor, c-Met, were revealed in the tooth germ of rat mandibular molars using RT-PCR. In situ hybridization demonstrated that the HGF gene was expressed only in the cells of the dental papilla of the tooth germ in vivo. The characteristic temporospatial distribution of HGF and c-Met during germ development was revealed using immunohistochemical studies in vivo. In order to demonstrate the functional role played by HGF in tooth development, HGF translation arrest by antisense phosphorothioate oligodeoxynucleotide (ODN) was carried out in vitro. In the control experiment, explants of tooth germs from embryonic 14 day mice were cultured in a modification of Trowell's system under serum-free and chemically defined conditions for two weeks. Other explants were cultured with 15mer antisense or sense ODN targeted to the HGF mRNA. Both the control and the sense-treated explants showed normal histological structure, as observed in vivo. On the other hand, antisense-treated explants exhibited an abnormal structure in which the enamel organs were surrounded by a thin layer of dentin and dental papilla, appearing ‘inside-out’ compared to the control and sense-treated explants, although the cytodifferentiation of ameloblasts and odontoblasts was not inhibited. The explants treated with recombinant human HGF combined with antisense ODN showed normal development, indicating that exogenous HGF rescued the explants from the abnormal structure caused by antisense ODN. The findings of a BrdU incorporation experiment suggested that the imbalance between the proliferation activity of the inner enamel epithelium and that of the dental papilla caused by HGF translation arrest results in the abnormal structure of the tooth germ. These results indicate that HGF is involved in the morphogenesis of the murine molar.

Amelogenesis imperfecta: Next-generation sequencing sheds light on Witkop’s classification

“…Enamel defects have also been reported in others syndromes and the question remains to qualify them as amelogenesis imperfecta. For instance, genes associated with -skin, nails and hair defects among other symptoms are ATR (Tanaka et al, 2012), CLDN1 (Feldmeyer et al, 2006), COG6 (Shaheen et al, 2013), FGF10, FGFR3, FGFR2 (Hollister et al, 1973), HRAS (Goodwin et al, 2014), KRAS, NRAS, KRT14 (Tabata et al, 1996), MBTPS2 (Martino et al, 1992); -with eye defects NAA10; -with skeletal anomalies AKT1, B3GAT3, CYP27B1, CTSK, EVC1, EVC2, ERCC4, ERCC8, GJA1, GNAS, IDUA, IRX5, NDN, PTDSS1, SNORD116, RUNX2, TBCE, VDR; -genito-urinary anomalies HNF1B, VPS33B, VIPAR; -intellectual disability PSPA, GALC; Usher syndrome MYO7A, USH2A, PD2D7, ADGRV1, CLRN1.…”

Hepatocyte Growth Factor Promotes Differentiation Potential and Stress Response of Human Stem Cells from Apical Papilla

“…In contrast to WNT, BMP/TGFβ, FGF, and HH, HGF/MET expression emerges later and covers less stages of tooth development. Temporospatial expression pattern of HGF and its receptor MET in tooth germ ranges from the early cap stage through the late bell stage [Tabata et al, 1996]. During the bell stage, HGF mRNA expression has been detected in the mesenchyme and dental papilla but not in the epithelium.…”