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 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(+).
Haze
Amir
A
Institute of Dental Sciences, Hebrew University - Hadassah, Jerusalem, Israel.
Taylor
Angela L
AL
Haegewald
Stefan
S
Leiser
Yoav
Y
Shay
Boaz
B
Rosenfeld
Eli
E
Gruenbaum-Cohen
Yael
Y
Dafni
Leah
L
Zimmermann
Bernd
B
Heikinheimo
Kristiina
K
Gibson
Carolyn W
CW
Fisher
Larry W
LW
Young
Marian F
MF
Blumenfeld
Anat
A
Bernimoulin
Jean P
JP
Deutsch
Dan
D
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
D053523:Amelogenin; D011994:Recombinant Proteins