Amelogenins are the most abundant
extracellular matrix proteins secreted by ameloblasts during tooth development and are important for enamel formation. Recently,
amelogenins have been detected not only in ameloblasts, which are differentiated from the epithelial cell lineage, but also in other tissues, including mesenchymal tissues at low levels, suggesting that
amelogenins possess other functions in these tissues. The therapeutic application of an enamel matrix derivative rich in
amelogenins resulted in the regeneration of cementum, alveolar bone, and periodontal ligament (PDL) in the treatment of experimental or human
periodontitis, indicating the attractive potential of
amelogenin in hard tissue formation. In addition, a full-length
amelogenin (M180) and
leucine-rich amelogenin peptide (
LRAP) regulate cementoblast/PDL cell proliferation and migration in vitro. Interestingly,
amelogenin null mice show increased osteoclastogenesis and
root resorption in periodontal tissues. Recombinant
amelogenin proteins suppress osteoclastogenesis in vivo and in vitro, suggesting that
amelogenin is involved in preventing idiopathic
root resorption.
Amelogenins are implicated in tissue-specific epithelial-mesenchymal or mesenchymal-mesenchymal signaling; however, the precise molecular mechanism has not been characterized. In this review, we first discuss the emerging evidence for the additional roles of M180 and
LRAP as signaling molecules in mesenchymal cells. Next, we show the results of a yeast two-hybrid assay aimed at identifying protein-binding partners for
LRAP. We believe that gaining further insights into the signaling pathway modulated by the multifunctional
amelogenin proteins will lead to the development of new therapeutic approaches for treating
dental diseases and disorders.