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Amelogenin

This protein of 28 kDa is encoded and expressed by genes on the Y chromosome (abbr. AMGY, AMELY; amelogenin Y) and the X chromosome (AMGX, AMELX; amelogenin X) (Lau et al, 1989; Salido et al, 1992; Nakahori et al, 1991). In the mouse, the Amelogenin gene appears to be located on the X chromosome only (Chapman et al, 1991). The protein encoded by the X chromosome gene differs from that encoded by the Y chromosome protein by a deletion of a methionine at codon 29 (Catalano-Sherman et al, 1993). Various slice variants of amelogenin have been reported (Bartlett et al, 2006; Gibson et al, 1991; Bonass et al, 1992).

Amelogenin is a highly conserved protein secreted by ameloblasts. It constitutes 90 % of the organic matrix of the outermost covering of the teeth, enamel and plays a role in regulating enamel biomineralization. Amelogenin may be a growth factor for periodontal ligament cells and also increases cell attachment. It modulates bone morphogenetic protein expression, downregulates the expression of collagen type 1, and induces expression of osteocalcin and bone sialoprotein, suggesting a role during periodontium development and regeneration (Zeichner-David et al, 2006).

Nishiguchi et al (2007) have reported that Amelogenin is a negative regulator of osteoclastogenesis via downregulation of RANKL, M-CSF and fibronectin expression in osteoblasts.

Lyngstadaas et al (1995) have demonstrated that in vivo knock-out of amelogenin expression by means of suitable ribozymes causes abnormally mineralized enamel. Knock-out mice lacking expression of the amelogenin gene show the phenotype of X-linked amelogenesis imperfecta, a phenotypically diverse hereditary disorder affecting enamel development that is caused by deletions or point mutations in the human X-chromosomal amelogenin gene. These mice display distinctly abnormal teeth with disorganized hypoplastic enamel. Their phenotype also shows that amelogenins are not required for the initiation of mineral crystal formation but rather for the organization of crystal pattern and regulation of enamel thickness (Gibson et al, 2001). Knock-out mice also show enhanced osteoclast formation and resorption of tooth cementum. Hatakeyama et L (2003) have shown that cementum defects are characterized by an increased presence of multinucleated cells, osteoclasts, and cementicles. These defects are associated with an increased expression of RANKL, a critical regulator of osteoclastogenesis.

LRAP [leucine-rich amelogenin polypeptide] (Fincham et al, 1981) is a peptide arising from alternative splicing of the amelogenin gene (Gibson et al, 1991; Bonass et al, 1992). Le et al (2006) and Habelitz et al (2006) have reported that full-length amelogenin and LRAP show calcium binding and structural differences, suggesting that these proteins have different functions in enamel biomineralization.

Hatakeyama et al (2006) have shown that LRAP and also full-length amelogenin regulate osteoclastogenesis and promote proliferation and migration of cementoblasts and periodontal ligament cells.

LRAP has no effect on cementoblast proliferation. LRAP downregulates osteocalcin and upregulates osteopontin expression, and inhibits mineral nodule formation. LRAP also increases expression of the osteoprotegerin gene but does not affect expression of RANKL (Bobaid et al, 2004). Ravindranath et al (2007) have suggested that LRAP may play a role in the differentiation of ameloblasts, growth of enamel and formation of dentinal tubules. Ye et al (2006) have shown that low-molecular-weight amelogenins, but not full-length amelogenin can enhance pulp cell proliferation.

The peptide has no effect on cell proliferation in cultures of human primary enamel epithelial cells, but promotes differentiation. Exogenously added peptide alters cell morphology, increases amelogenin synthesis, downregulates Notch-1 expression, and increases expression of LAMP-1, a membrane receptor for LRAP in mesenchymal cells (Le et al, 2007)

Chen et al (2003) have created a transgenic mouse that expresses bovine LRAP in the enamel-secreting ameloblast cells of the dental organ. Crosses with amelogenin knock-out mice, which make none of the amelogenin proteins and have a severe hypoplastic and disorganized enamel phenotype demonstrate that LRAP cannot rescue the enamel defect in amelogenin knock-out mice.

Warotayanont et al (2008) have reported that LRAP has a unique function during embryonic stem cell differentiation along osteogenic lineage. LRAP treatment of wild-type and amelogenin knock-out embryonic stem cells induces a significant increase in mineral matrix formation, and significant increases in bone sialoprotein and osterix gene expression. The amelogenin knock-out phenotype is rescued partially by the addition of exogenous LRAP.

TRAP [tyrosine-rich amelogenin polypeptide] is a proteolytic fragment of amelogenin and appears to exist in various terminally extended forms (Fincham et al, 1981, 1989). Swanson et al (2006) have reported that TRAP downregulates the expression of osteocalcin, osteopontin, and bone sialoprotein, and induces mineral nodule formation in cementoblasts. Paine et al (2004) have reported that overexpression of TRAP in the enamel matrix does not alter the enamel structural hierarchy.

Li et al (2003) have suggested that a reduced rate of TRAP formation may alter enamel matrix hydrolysis by the metalloproteinase MMP-20, which may result in amelogenesis imperfecta.

LAST MODIFIED: March 2008

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