Amelogenin: A Potential Regulator of Cementum‐Associated Genes

Background: Studies suggest that enamel matrix proteins induce differentiation and mineralization of a variety of mesenchymal cells, including odontoblasts, osteoblasts, and cementoblasts. It has been postulated that this activity could be due to amelogenin‐like proteins, known to be present in some mixtures of enamel matrix derivatives. Amelogenins have been reported to induce expression of a mineralized tissue‐specific marker, bone sialoprotein (BSP), indicating that epithelial products can regulate the activity of mesenchyme‐derived cells. Methods: To explore the molecular mechanisms involved in BSP regulation, a clonal population of immortalized murine cementoblasts (OCCM‐30) was exposed to full‐length murine amelogenin protein (rp(H)M180), 0.1 µg/ml to 10.0 µg/ml, for 8 days in vitro. To further investigate the potential epithelial‐mesenchymal interaction, an amelogenin knockout mouse model was used to examine expression of BSP and other markers, including Type I collagen, in tissue samples. Results: The lowest dose of amelogenin slightly enhanced BSP expression, whereas at the highest dose, a dramatic decrease (three‐fold) in BSP expression was observed. Parallel experiments showed a corresponding decrease in mineral nodule formation in vitro for cells treated with the higher dose of rp(H)M180. In situ hybridization and immunohistochemical analysis of sections from amelogenin null mice revealed a dramatic reduction in expression of BSP mRNA and protein in cementoblasts and surrounding osteoblasts in comparison to age‐matched controls. In contrast, the expression of Type I collagen was not significantly different from controls. Conclusion: These data suggest that amelogenin may be a critical signaling molecule required for appropriate development of the periodontium. J Periodontol 2003;74:1423‐1431.