Expression of hepatocyte growth factor/scatter factor and c-Met in human dental papilla and fibroblasts from dental papilla

Hepatocyte growth factor/scatter factor (HGF/SF), a broad-spectrum and mult ifunctional cytokine, is essential for the development of tissues including tooth. Here it was found that the HGF/SF content of human dental papillae obtained from 8 to 16-year-old individuals decreased significantly with age . Cultured fibroblasts prepared fi-om the dental papillae of individuals of different ages produced HGF/SF at almost the yams rate, but the sensitivit ies of the cells to interleukin-1 alpha and tumour necrosis factor-alpha fo r the production of HGF/SF increased with age. Generally, mesenchymal cells such as fibroblasts produce HGF/SF but do not express c-Met, a receptor fo r HGF/SF, yet fibroblasts in dental papilla and cultured fibroblasts prepar ed from dental papilla did express c-Met, as determined by immunohistochemi cally, in situ hybridization and reverse transcription-polymerase chain rea ction. Recombinant human [I-125]iodo-HGF/SF specifically bound to cell-surf ace macromolecules with a mol. wt of 146,000, which is the same as that of the beta-subunit of c-Met. The physiological role of c-Met on fibroblasts i n dental papilla is unknown, but the addition of 2 ng of HGF/SF per ml to t he culture medium significantly stimulated DNA synthesis in the cells, us d etermined by pulse labelling with [H-3]thymidine. Exogenous HGF/SF also sti mulated secretion by the cells of vascular endothelial growth factor, a cyt okine that induces blood vessel-formation. These results suggest that HGF/S F may be involved in tooth development via autocrine mechanisms. (C) 1999 E lsevier Science Ltd. All rights reserved.