Regeneration of bone and periodontal ligament induced by recombinant amelogenin after periodontitis

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 199...

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Published in:Journal of cellular and molecular medicine 2009-06, Vol.13 (6), p.1110-1124
Main Authors: Haze, Amir, Taylor, Angela L., Haegewald, Stefan, Leiser, Yoav, Shay, Boaz, Rosenfeld, Eli, Gruenbaum‐Cohen, Yael, Dafni, Leah, Zimmermann, Bernd, Heikinheimo, Kristiina, Gibson, Carolyn W., Fisher, Larry W., Young, Marian F., Blumenfeld, Anat, Bernimoulin, Jean P., Deutsch, Dan
Format: Article
Language:English
Subjects:
Alveolar bone
Alveolar Process - metabolism
Alveolar Process - physiopathology
amelogenin
Amelogenin - genetics
Amelogenin - metabolism
Amelogenin - pharmacology
Animals
Bone growth
Bone loss
bone regeneration
Bone Regeneration - drug effects
Bone turnover
Bones
CD105
Cell differentiation
Cell Line
Cementum
cementum regeneration
Dental Cementum - drug effects
Dental Cementum - metabolism
Dental Cementum - physiopathology
Dental enamel
Disease Models, Animal
Dog Diseases - genetics
Dog Diseases - metabolism
Dog Diseases - physiopathology
Dogs
Extracellular matrix
Female
Genes
Genetic recombination
Gum disease
Humans
Hydrophobicity
Immunohistochemistry
In Situ Hybridization
Ligaments
Mutation
Osteoclasts
Osteocytes
Osteoprogenitor cells
PDL regeneration
Peptides
periodontal disease
Periodontal ligament
Periodontal Ligament - drug effects
Periodontal Ligament - metabolism
Periodontal Ligament - physiopathology
Periodontitis
Periodontitis - physiopathology
Periodontitis - veterinary
Polypeptides
Progenitor cells
Proteins
Rats
Recombinant Proteins - metabolism
Recombinant Proteins - pharmacology
Regeneration
Regeneration - drug effects
Spodoptera
Stem cells
Stromal cells
STRO‐1
Surgery
Teeth
Temporal variations
Tissues
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Summary: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+.
ISSN:1582-1838
1582-4934
DOI:10.1111/j.1582-4934.2009.00700.x