title: Regeneration of bone and periodontal ligament induced by recombinant amelogenin after periodontitis.
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(+).
authors.affiliation: Institute of Dental Sciences, Hebrew University - Hadassah, Jerusalem, Israel.
authors.forename: Amir
authors.initials: A
authors.lastname: Haze
authors.forename: Angela L
authors.initials: AL
authors.lastname: Taylor
authors.forename: Stefan
authors.initials: S
authors.lastname: Haegewald
authors.forename: Yoav
authors.initials: Y
authors.lastname: Leiser
authors.forename: Boaz
authors.initials: B
authors.lastname: Shay
authors.forename: Eli
authors.initials: E
authors.lastname: Rosenfeld
authors.forename: Yael
authors.initials: Y
authors.lastname: Gruenbaum-Cohen
authors.forename: Leah
authors.initials: L
authors.lastname: Dafni
authors.forename: Bernd
authors.initials: B
authors.lastname: Zimmermann
authors.forename: Kristiina
authors.initials: K
authors.lastname: Heikinheimo
authors.forename: Carolyn W
authors.initials: CW
authors.lastname: Gibson
authors.forename: Larry W
authors.initials: LW
authors.lastname: Fisher
authors.forename: Marian F
authors.initials: MF
authors.lastname: Young
authors.forename: Anat
authors.initials: A
authors.lastname: Blumenfeld
authors.forename: Jean P
authors.initials: JP
authors.lastname: Bernimoulin
authors.forename: Dan
authors.initials: D
authors.lastname: Deutsch
mesh_terms: D000539:Alveolar Process / Q000378:metabolism / Q000503:physiopathology; D053523:Amelogenin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D002460:Cell Line; D003739:Dental Cementum / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004283:Dog Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D004285:Dogs; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D010513:Periodontal Ligament / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D010518:Periodontitis / Q000503:physiopathology / Q000662:veterinary*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D012038:Regeneration / Q000187:drug effects; D018411:Spodoptera
chemical_list: D053523:Amelogenin; D011994:Recombinant Proteins