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Ameloblastin is a cell adhesion molecule required for maintaining the differentiation state of ameloblasts.

Fukumoto S, Kiba T, Hall B, Iehara N, Nakamura T, Longenecker G, Krebsbach PH, Nanci A, Kulkarni AB, Yamada Y - J. Cell Biol. (2004)

Bottom Line: Tooth morphogenesis results from reciprocal interactions between oral epithelium and ectomesenchyme culminating in the formation of mineralized tissues, enamel, and dentin.We found that recombinant ameloblastin adhered specifically to ameloblasts and inhibited cell proliferation.Thus, ameloblastin is a cell adhesion molecule essential for amelogenesis, and it plays a role in maintaining the differentiation state of secretory stage ameloblasts by binding to ameloblasts and inhibiting proliferation.

View Article: PubMed Central - PubMed

Affiliation: Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.

ABSTRACT
Tooth morphogenesis results from reciprocal interactions between oral epithelium and ectomesenchyme culminating in the formation of mineralized tissues, enamel, and dentin. During this process, epithelial cells differentiate into enamel-secreting ameloblasts. Ameloblastin, an enamel matrix protein, is expressed by differentiating ameloblasts. Here, we report the creation of ameloblastin- mice, which developed severe enamel hypoplasia. In mutant tooth, the dental epithelium differentiated into enamel-secreting ameloblasts, but the cells were detached from the matrix and subsequently lost cell polarity, resumed proliferation, and formed multicell layers. Expression of Msx2, p27, and p75 were deregulated in mutant ameloblasts, the phenotypes of which were reversed to undifferentiated epithelium. We found that recombinant ameloblastin adhered specifically to ameloblasts and inhibited cell proliferation. The mutant mice developed an odontogenic tumor of dental epithelium origin. Thus, ameloblastin is a cell adhesion molecule essential for amelogenesis, and it plays a role in maintaining the differentiation state of secretory stage ameloblasts by binding to ameloblasts and inhibiting proliferation.

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Tumor formation in mutant mice. (A) Tumor appearance in 36-wk-old homozygous ameloblastin- mouse. Tumors were observed only on the right side of the maxillar of mutant mice. Right panel shows micro X-ray radiographs by Faxitron. Arrow and arrowheads indicate tumor. (B) Frequency of tumor formation with age. The earliest tumor was observed at 26 wk old. Only one heterozygous mouse developed a tumor. (C) Hematoxylin-eosin staining of tumor lesion of 36-wk-old mutant moue shown in A. Dotted lines indicate tumor lesions and the boxed area is enlarged at the bottom panel. (D) Immunostaining of tumor lesions. Top panel shows immunostaining of focal area and bottom panel shows surrounding cells. The focal area is stained with antibodies to enamel matrix proteins except ameloblastin, indicating accumulation of enamel matrix proteins. Cells surrounding focal areas are immunopositive for enamel matrix proteins, suggesting ameloblast origin. AMBN, ameloblastin; AMEL, amelogenin; ENAM, enamelin; int α6, integrin α6. (E) RT-PCR analysis of RNA from tumor lesions. RNA samples for lanes +/− and −/− were from dental epithelium of P7 molar of homozygous and heterozygous mice, respectively. RNA of lanes T1 and T2 was from tumor lesions of 39- and 51-wk-old homozygous mice. RNA of lane T3 was from a 51-wk-old heterozygous mouse. Note: heterozygous mouse did not express ameloblastin mRNA in the tumor but expressed mRNA for other enamel matrix proteins similar to the homozygous mice.
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fig8: Tumor formation in mutant mice. (A) Tumor appearance in 36-wk-old homozygous ameloblastin- mouse. Tumors were observed only on the right side of the maxillar of mutant mice. Right panel shows micro X-ray radiographs by Faxitron. Arrow and arrowheads indicate tumor. (B) Frequency of tumor formation with age. The earliest tumor was observed at 26 wk old. Only one heterozygous mouse developed a tumor. (C) Hematoxylin-eosin staining of tumor lesion of 36-wk-old mutant moue shown in A. Dotted lines indicate tumor lesions and the boxed area is enlarged at the bottom panel. (D) Immunostaining of tumor lesions. Top panel shows immunostaining of focal area and bottom panel shows surrounding cells. The focal area is stained with antibodies to enamel matrix proteins except ameloblastin, indicating accumulation of enamel matrix proteins. Cells surrounding focal areas are immunopositive for enamel matrix proteins, suggesting ameloblast origin. AMBN, ameloblastin; AMEL, amelogenin; ENAM, enamelin; int α6, integrin α6. (E) RT-PCR analysis of RNA from tumor lesions. RNA samples for lanes +/− and −/− were from dental epithelium of P7 molar of homozygous and heterozygous mice, respectively. RNA of lanes T1 and T2 was from tumor lesions of 39- and 51-wk-old homozygous mice. RNA of lane T3 was from a 51-wk-old heterozygous mouse. Note: heterozygous mouse did not express ameloblastin mRNA in the tumor but expressed mRNA for other enamel matrix proteins similar to the homozygous mice.

Mentions: We observed that mutant mice developed soft tissue tumors in the buccal vestibule of the maxilla with age (Fig. 8 A). About 19% of the homozygous mice (6 out of 32 mice) developed lesions, with the earliest occurrence at 26 wk old (Fig. 8 B). The soft tissue tumors consisted of small epithelioid cells expressing integrin α6 and enamel matrix proteins, including amelogenin, enamelin, and tuftelin (Fig. 8, C and D). The atypical epithelium surrounded focal areas of necrotic tissue with condensed matrix staining containing calcospherites at the center. There was no ameloblastin staining in either the cells or the matrix structure. Less amelogenin staining was observed compared with other matrix proteins consistent with the expression pattern in mutant teeth. RT-PCR analysis of tumor tissue revealed expression of mRNA for enamel matrix proteins including amelogenin, enamelin, and tuftelin (Fig. 8 E). These results indicate that the tumors are derived from dental epithelium. We found that only one heterozygous mouse (1 out of 48) developed a tumor. Immunostaining (unpublished data) and RT-PCR revealed that the tumor in this heterozygous mouse did not express ameloblastin but did express other enamel matrix proteins. These cells had apparently gained the ameloblastin- phenotype that resulted in unregulated cell proliferation.


Ameloblastin is a cell adhesion molecule required for maintaining the differentiation state of ameloblasts.

Fukumoto S, Kiba T, Hall B, Iehara N, Nakamura T, Longenecker G, Krebsbach PH, Nanci A, Kulkarni AB, Yamada Y - J. Cell Biol. (2004)

Tumor formation in mutant mice. (A) Tumor appearance in 36-wk-old homozygous ameloblastin- mouse. Tumors were observed only on the right side of the maxillar of mutant mice. Right panel shows micro X-ray radiographs by Faxitron. Arrow and arrowheads indicate tumor. (B) Frequency of tumor formation with age. The earliest tumor was observed at 26 wk old. Only one heterozygous mouse developed a tumor. (C) Hematoxylin-eosin staining of tumor lesion of 36-wk-old mutant moue shown in A. Dotted lines indicate tumor lesions and the boxed area is enlarged at the bottom panel. (D) Immunostaining of tumor lesions. Top panel shows immunostaining of focal area and bottom panel shows surrounding cells. The focal area is stained with antibodies to enamel matrix proteins except ameloblastin, indicating accumulation of enamel matrix proteins. Cells surrounding focal areas are immunopositive for enamel matrix proteins, suggesting ameloblast origin. AMBN, ameloblastin; AMEL, amelogenin; ENAM, enamelin; int α6, integrin α6. (E) RT-PCR analysis of RNA from tumor lesions. RNA samples for lanes +/− and −/− were from dental epithelium of P7 molar of homozygous and heterozygous mice, respectively. RNA of lanes T1 and T2 was from tumor lesions of 39- and 51-wk-old homozygous mice. RNA of lane T3 was from a 51-wk-old heterozygous mouse. Note: heterozygous mouse did not express ameloblastin mRNA in the tumor but expressed mRNA for other enamel matrix proteins similar to the homozygous mice.
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fig8: Tumor formation in mutant mice. (A) Tumor appearance in 36-wk-old homozygous ameloblastin- mouse. Tumors were observed only on the right side of the maxillar of mutant mice. Right panel shows micro X-ray radiographs by Faxitron. Arrow and arrowheads indicate tumor. (B) Frequency of tumor formation with age. The earliest tumor was observed at 26 wk old. Only one heterozygous mouse developed a tumor. (C) Hematoxylin-eosin staining of tumor lesion of 36-wk-old mutant moue shown in A. Dotted lines indicate tumor lesions and the boxed area is enlarged at the bottom panel. (D) Immunostaining of tumor lesions. Top panel shows immunostaining of focal area and bottom panel shows surrounding cells. The focal area is stained with antibodies to enamel matrix proteins except ameloblastin, indicating accumulation of enamel matrix proteins. Cells surrounding focal areas are immunopositive for enamel matrix proteins, suggesting ameloblast origin. AMBN, ameloblastin; AMEL, amelogenin; ENAM, enamelin; int α6, integrin α6. (E) RT-PCR analysis of RNA from tumor lesions. RNA samples for lanes +/− and −/− were from dental epithelium of P7 molar of homozygous and heterozygous mice, respectively. RNA of lanes T1 and T2 was from tumor lesions of 39- and 51-wk-old homozygous mice. RNA of lane T3 was from a 51-wk-old heterozygous mouse. Note: heterozygous mouse did not express ameloblastin mRNA in the tumor but expressed mRNA for other enamel matrix proteins similar to the homozygous mice.
Mentions: We observed that mutant mice developed soft tissue tumors in the buccal vestibule of the maxilla with age (Fig. 8 A). About 19% of the homozygous mice (6 out of 32 mice) developed lesions, with the earliest occurrence at 26 wk old (Fig. 8 B). The soft tissue tumors consisted of small epithelioid cells expressing integrin α6 and enamel matrix proteins, including amelogenin, enamelin, and tuftelin (Fig. 8, C and D). The atypical epithelium surrounded focal areas of necrotic tissue with condensed matrix staining containing calcospherites at the center. There was no ameloblastin staining in either the cells or the matrix structure. Less amelogenin staining was observed compared with other matrix proteins consistent with the expression pattern in mutant teeth. RT-PCR analysis of tumor tissue revealed expression of mRNA for enamel matrix proteins including amelogenin, enamelin, and tuftelin (Fig. 8 E). These results indicate that the tumors are derived from dental epithelium. We found that only one heterozygous mouse (1 out of 48) developed a tumor. Immunostaining (unpublished data) and RT-PCR revealed that the tumor in this heterozygous mouse did not express ameloblastin but did express other enamel matrix proteins. These cells had apparently gained the ameloblastin- phenotype that resulted in unregulated cell proliferation.

Bottom Line: Tooth morphogenesis results from reciprocal interactions between oral epithelium and ectomesenchyme culminating in the formation of mineralized tissues, enamel, and dentin.We found that recombinant ameloblastin adhered specifically to ameloblasts and inhibited cell proliferation.Thus, ameloblastin is a cell adhesion molecule essential for amelogenesis, and it plays a role in maintaining the differentiation state of secretory stage ameloblasts by binding to ameloblasts and inhibiting proliferation.

View Article: PubMed Central - PubMed

Affiliation: Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.

ABSTRACT
Tooth morphogenesis results from reciprocal interactions between oral epithelium and ectomesenchyme culminating in the formation of mineralized tissues, enamel, and dentin. During this process, epithelial cells differentiate into enamel-secreting ameloblasts. Ameloblastin, an enamel matrix protein, is expressed by differentiating ameloblasts. Here, we report the creation of ameloblastin- mice, which developed severe enamel hypoplasia. In mutant tooth, the dental epithelium differentiated into enamel-secreting ameloblasts, but the cells were detached from the matrix and subsequently lost cell polarity, resumed proliferation, and formed multicell layers. Expression of Msx2, p27, and p75 were deregulated in mutant ameloblasts, the phenotypes of which were reversed to undifferentiated epithelium. We found that recombinant ameloblastin adhered specifically to ameloblasts and inhibited cell proliferation. The mutant mice developed an odontogenic tumor of dental epithelium origin. Thus, ameloblastin is a cell adhesion molecule essential for amelogenesis, and it plays a role in maintaining the differentiation state of secretory stage ameloblasts by binding to ameloblasts and inhibiting proliferation.

Show MeSH
Related in: MedlinePlus