Ameloblastin promotes bone growth by enhancing proliferation of progenitor cells and by stimulating immunoregulators.
In this study, we examined the role of the enamel matrix protein, ameloblastin, in bone growth and remodelling, and attempted to identify some of the molecular mechanisms involved in these processes. The effects of recombinant ameloblastin (rAmbn) were tested in vivo in rats, and in vitro in primary human mesenchymal stem cells, osteoblasts, chondrocytes, and osteoclasts. We used a microarray technique to identify genes that were regulated in human osteoblasts and verified our findings using multiplex protein analysis and real-time RT-PCR. Recombinant ameloblastin was found to stimulate bone healing in vivo, and to enhance the proliferation of mesenchymal stem cells and osteoblasts, as well as the differentiation of osteoclast precursor cells in vitro. The most profound effect was on the regulation of genes related to immune responses as well as on the expression of cytokines and markers of bone cell differentiation, indicating that ameloblastin has an effect on mesenchymal cell differentiation. A receptor has not yet been identified, but we found rAmbn to induce, directly and indirectly, signal transducer and activator of transcription (STAT) 1 and 2 and downstream factors in the interferon pathway.
Tamburstuen
Margareth V
MV
Department of Biomaterials, Faculty of Dentistry, University of Oslo (UiO), Oslo, Norway.
Reppe
Sjur
S
Spahr
Axel
A
Sabetrasekh
Roya
R
Kvalheim
Gunnar
G
Slaby
Ivan
I
Syversen
Unni
U
Lyngstadaas
Staale Petter
SP
Reseland
Janne E
JE
D000704:Analysis of Variance; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003746:Dental Enamel Proteins / Q000494:pharmacology / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism*; D007372:Interferons / Q000096:biosynthesis* / Q000235:genetics; D008334:Mandible / Q000166:cytology / Q000601:surgery; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D050794:STAT1 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D050795:STAT2 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D018709:Statistics, Nonparametric
C490889:AMBN protein, human; D003746:Dental Enamel Proteins; D007155:Immunologic Factors; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D007372:Interferons