Amelogenin: a potential regulator of cementum-associated genes.
BACKGROUND
Studies suggest that enamel matrix proteins induce differentiation and mineralization of a variety of mesenchymal cells, including odontoblasts, osteoblasts, and cementoblasts. It has been postulated that this activity could be due to amelogenin-like proteins, known to be present in some mixtures of enamel matrix derivatives. Amelogenins have been reported to induce expression of a mineralized tissue-specific marker, bone sialoprotein (BSP), indicating that epithelial products can regulate the activity of mesenchyme-derived cells.


METHODS
To explore the molecular mechanisms involved in BSP regulation, a clonal population of immortalized murine cementoblasts (OCCM-30) was exposed to full-length murine amelogenin protein (rp(H)M180), 0.1 microg/ml to 10.0 microg/ml, for 8 days in vitro. To further investigate the potential epithelial-mesenchymal interaction, an amelogenin knockout mouse model was used to examine expression of BSP and other markers, including Type I collagen, in tissue samples.


RESULTS
The lowest dose of amelogenin slightly enhanced BSP expression, whereas at the highest dose, a dramatic decrease (three-fold) in BSP expression was observed. Parallel experiments showed a corresponding decrease in mineral nodule formation in vitro for cells treated with the higher dose of rp(H)M180. In situ hybridization and immunohistochemical analysis of sections from amelogenin null mice revealed a dramatic reduction in expression of BSP mRNA and protein in cementoblasts and surrounding osteoblasts in comparison to age-matched controls. In contrast, the expression of Type I collagen was not significantly different from controls.


CONCLUSIONS
These data suggest that amelogenin may be a critical signaling molecule required for appropriate development of the periodontium.
Viswanathan
Hema L
HL
Department of Periodontics, Prevention and Geriatrics, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
Berry
Janice E
JE
Foster
Brian L
BL
Gibson
Carolyn W
CW
Li
Yong
Y
Kulkarni
Ashok B
AB
Snead
Malcolm L
ML
Somerman
Martha J
MJ
D053523:Amelogenin; D000704:Analysis of Variance; D000818:Animals; D015152:Blotting, Northern; D002454:Cell Differentiation; D002478:Cells, Cultured; D025021:Cementogenesis / Q000235:genetics*; D024042:Collagen Type I / Q000096:biosynthesis; D003739:Dental Cementum / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D003746:Dental Enamel Proteins / Q000235:genetics* / Q000494:pharmacology; D004847:Epithelial Cells / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D017403:In Situ Hybridization; D058574:Integrin-Binding Sialoprotein; D008648:Mesoderm / Q000166:cytology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D015675:Osteocalcin / Q000096:biosynthesis; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D018709:Statistics, Nonparametric
D053523:Amelogenin; C507200:Amelx protein, mouse; D024042:Collagen Type I; D003746:Dental Enamel Proteins; C546872:Ibsp protein, mouse; D058574:Integrin-Binding Sialoprotein; D012795:Sialoglycoproteins; D015675:Osteocalcin