The role of BMP4 in HERS during tooth root development

Tooth development is regulated by reciprocal interactions between epithelial and mesenchymal cells. Several morphological studies suggest that growth factors secreted from these cells regulate tooth development. These growth factors induce undifferentiated cells in the tooth germ to differentiate into tooth-forming cells. Many growth factors are reportedly expressed in the developing tooth, but the key molecule underlying tooth root development is still unknown. There is a considerable amount of data on the expression and function of bone morphogenetic proteins (BMPs) during tooth development, but the relationship between BMPs and tooth root development has not been analyzed extensively. This prompted us to examine the expression patterns of BMP4 and BMP receptors (BMPRs) at the apical region of the tooth germ during mouse tooth root development. We found that BMP4 was strictly expressed in the apical mesenchyme, and that BMPRs were localized in Hertwig's epithelial root sheath (HERS). We also investigated the possible roles of BMP4 in HERS during the early stage of tooth root development. Our organ-culture results indicated that BMP4 regulates HERS formation via harmonious interactions with its own antagonist, noggin, by preventing elongation and maintaining cell proliferation. BMP4 may therefore be useful in various tissue-engineering applications as a regulator of tooth root formation.