Regeneration of bone and periodontal ligament induced by recombinant amelogenin after periodontitis |
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Authors: | Amir Haze Angela L Taylor Stefan Haegewald Yoav Leiser Boaz Shay Eli Rosenfeld Yael Gruenbaum-Cohen Leah Dafni Bernd Zimmermann Kristiina Heikinheimo Carolyn W Gibson Larry W Fisher Marian F Young Anat Blumenfeld Jean P Bernimoulin Dan Deutsch |
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Institution: | Dental Research Laboratory, Institute of Dental Sciences, Faculty of Dental Medicine, Hebrew University –Hadassah, Jerusalem, Israel;Department of Periodontology CharitèUniversitatsmediizin Berlin, Berlin, Germany;Institute of Anatomy, Charitè, Berlin, Germany;Department of Oral Maxillofacial Surgery, Institute of Dentistry, University of Turku, Turku, Finland;Department of Anatomy and Cell Biology, University of Pennsylvania School of Dental Medicine, Philadelphia, PA, USA;Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institute of Health, Bethesda, MD, USA |
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Abstract: | Regeneration of mineralized tissues affected by chronic diseases comprises a major scientific and clinical challenge. Periodontitis, one such prevalent disease, involves destruction of the tooth-supporting tissues, alveolar bone, periodontal-ligament and cementum, often leading to tooth loss. In 1997, it became clear that, in addition to their function in enamel formation, the hydrophobic ectodermal enamel matrix proteins (EMPs) play a role in the regeneration of these periodontal tissues. The epithelial EMPs are a heterogeneous mixture of polypeptides encoded by several genes. It was not clear, however, which of these many EMPs induces the regeneration and what mechanisms are involved. Here we show that a single recombinant human amelogenin protein (rHAM+), induced in vivo regeneration of all tooth-supporting tissues after creation of experimental periodontitis in a dog model. To further understand the regeneration process, amelogenin expression was detected in normal and regenerating cells of the alveolar bone (osteocytes, osteoblasts and osteoclasts), periodontal ligament, cementum and in bone marrow stromal cells. Amelogenin expression was highest in areas of high bone turnover and activity. Further studies showed that during the first 2 weeks after application, rHAM+ induced, directly or indirectly, significant recruitment of mesenchymal progenitor cells, which later differentiated to form the regenerated periodontal tissues. The ability of a single protein to bring about regeneration of all periodontal tissues, in the correct spatio-temporal order, through recruitment of mesenchymal progenitor cells, could pave the way for development of new therapeutic devices for treatment of periodontal, bone and ligament diseases based on rHAM+. |
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Keywords: | amelogenin periodontal disease bone regeneration cementum regeneration PDL regeneration CD105 STRO-1 |
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