title: BMP4 signaling regulates formation of Hertwig's epithelial root sheath during tooth root development.
abstract: Although Hertwig's epithelial root sheath (HERS) performs an important function in the formation of the tooth root, the developmental mechanisms that control HERS growth and differentiation remain to be thoroughly elucidated. Bone morphogenetic protein 4 (BMP4), which is secreted by mesenchymal cells, acts on the dental epithelium as a regulator of cell differentiation during crown formation. In an effort to determine whether BMP4 specifically regulates the development of HERS in the dental epithelium, we assessed the localizations of BMP4, BMP receptor-IB (BMPR-IB), and BMPR-II during molar root formation in the mouse. HERS cells were shown to express BMPR-IB and BMPR-II. BMP4-positive cells were detected densely in the dental papillae around HERS, thereby suggesting that BMP4 participated in HERS formation. Beads soaked in BMP4, NOGGIN, or phosphate-buffered saline (PBS) were implanted into the pulp cavity under culture conditions, and the length of HERS was evaluated with regard to the proliferating cells. After 12 h, both groups exhibited a similar HERS developmental pattern, with the length and shape of HERS bearing a close resemblance to one another. However, after 48 h, the observed HERS elongation was significantly shorter in the BMP4-treated group. In addition, proliferative cell nuclear antigens were detectable only in the NOGGIN- and PBS-treated groups. These findings demonstrate that mesenchymally expressed BMP4 regulates HERS development by preventing elongation and maintaining cell proliferation. BMP4 may, therefore, prove useful as a root-formation regulatory agent in a variety of tissue-engineering applications.
authors.affiliation: Division in Anatomy and Developmental Biology, Department of Oral Biology, Research Center for Orofacial Hard Tissue Regeneration, Brain Korea 21 Project, Yonsei University College of Dentistry, Seodaemun-gu, Seoul, Republic of Korea.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hosoya
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Kim
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Cho
authors.forename: Han-Sung
authors.initials: HS
authors.lastname: Jung
mesh_terms: D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D052004:Bone Morphogenetic Protein Receptors / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008813:Mice, Inbred ICR; D009804:Odontoblasts / Q000166:cytology / Q000378:metabolism; D009924:Organ Culture Techniques; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D014092:Tooth Root / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D000099176:Noggin Protein
chemical_list: D055415:Bone Morphogenetic Protein 4; D052004:Bone Morphogenetic Protein Receptors; D002352:Carrier Proteins; D011994:Recombinant Proteins; D000099176:Noggin Protein; C525810:Bmp4 protein, mouse