Ameloblastin Fusion Protein Enhances Pulpal Healing and Dentin Formation in Porcine Teeth

Nakamura, Yukio; Slaby, Ivan; Spahr, Axel; Pezeshki, Gita; Matsumoto, Koukichi; Lyngstadaas, Ståle Petter

doi:10.1007/s00223-005-0144-2

Cited by 27 publications

(36 citation statements)

References 20 publications

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“…39–49 AMBN can enhance reparative dentin formation, which confirms that this protein has an important role in odontoblast differentiation and dentinogenesis. 50 The enamel defects confirm the observations from mouse models and show that human AI is associated with disrupted Ambn function. However, to date, mutations of AMBN have not been associated with the phenotypes of hereditary dentin disorders.…”

Section: Introductionsupporting

confidence: 75%

Whole exome sequencing identifies an AMBN missense mutation causing severe autosomal-dominant amelogenesis imperfecta and dentin disorders

Lü

et al. 2018

Int J Oral Sci

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Tooth development is a complex process that involves precise and time-dependent orchestration of multiple genetic, molecular, and cellular interactions. Ameloblastin (AMBN, also named “amelin” or “sheathlin”) is the second most abundant enamel matrix protein known to have a key role in amelogenesis. Amelogenesis imperfecta (AI [MIM: 104500]) refers to a genetically and phenotypically heterogeneous group of conditions characterized by inherited developmental enamel defects. The hereditary dentin disorders comprise a variety of autosomal-dominant genetic symptoms characterized by abnormal dentin structure affecting either the primary or both the primary and secondary teeth. The vital role of Ambn in amelogenesis has been confirmed experimentally using mouse models. Only two cases have been reported of mutations of AMBN associated with non-syndromic human AI. However, no AMBN missense mutations have been reported to be associated with both human AI and dentin disorders. We recruited one kindred with autosomal-dominant amelogenesis imperfecta (ADAI) and dentinogenesis imperfecta/dysplasia characterized by generalized severe enamel and dentin defects. Whole exome sequencing of the proband identified a novel heterozygous C-T point mutation at nucleotide position 1069 of the AMBN gene, causing a Pro to Ser mutation at the conserved amino acid position 357 of the protein. Exfoliated third molar teeth from the affected family members were found to have enamel and dentin of lower mineral density than control teeth, with thinner and easily fractured enamel, short and thick roots, and pulp obliteration. This study demonstrates, for the first time, that an AMBN missense mutation causes non-syndromic human AI and dentin disorders.

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Section: Introductionsupporting

confidence: 75%

Whole exome sequencing identifies an AMBN missense mutation causing severe autosomal-dominant amelogenesis imperfecta and dentin disorders

Lü

et al. 2018

Int J Oral Sci

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“…This inhibition is accompanied by the induction of p21 and p27 and ENAM and the reduction of Msx2. It was recently reported that AMBN fusion protein enhances pulpal healing and dentin formation in porcine teeth (21). In addition, AMBN promotes adhesion of periodontal ligament cells and modulates the expression of bone morphogenic protein, collagen type I, and osteocalcin (22).…”

Section: Discussionmentioning

confidence: 98%

“…These results suggest that enamel formation and rod morphology are influenced by temporal and spatial expressions of AMBN and imply that the AMBN gene locus may be involved in the etiology of a number of cases of undiagnosed hereditary amelogenesis imperfecta (8). Further, it was reported that recombinant AMBN enhances pulpal wound healing and reparative dentine formation following pulpotomy procedures, suggesting that it functions as a signal molecule in epithelial-mesenchymal interactions (9).…”

mentioning

confidence: 86%

Critical Role of Heparin Binding Domains of Ameloblastin for Dental Epithelium Cell Adhesion and Ameloblastoma Proliferation

Sonoda

Iwamoto

Nakamura

et al. 2009

Journal of Biological Chemistry

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AMBN (ameloblastin)is an enamel matrix protein that regulates cell adhesion, proliferation, and differentiation of ameloblasts. In AMBN-deficient mice, ameloblasts are detached from the enamel matrix, continue to proliferate, and form a multiple cell layer; often, odontogenic tumors develop in the maxilla with age. However, the mechanism of AMBN functions in these biological processes remains unclear. By using recombinant AMBN proteins, we found that AMBN had heparin binding domains at the C-terminal half and that these domains were critical for AMBN binding to dental epithelial cells. Overexpression of fulllength AMBN protein inhibited proliferation of human ameloblastoma AM-1 cells, but overexpression of heparin binding domain-deficient AMBN protein had no inhibitory effect. In full-length AMBN-overexpressing AM-1 cells, the expression of Msx2, which is involved in the dental epithelial progenitor phenotype, was decreased, whereas the expression of cell proliferation inhibitors p21 and p27 was increased. We also found that the expression of enamelin, a marker of differentiated ameloblasts, was induced, suggesting that AMBN promotes odontogenic tumor differentiation. Thus, our results suggest that AMBN promotes cell binding through the heparin binding sites and plays an important role in preventing odontogenic tumor development by suppressing cell proliferation and maintaining differentiation phenotype through Msx2, p21, and p27.The extracellular matrix provides structural support for cells and regulates cell proliferation, migration, differentiation, and apoptosis for tissue development and homeostasis (1). The extracellular matrix also plays a crucial role in pathological processes and diseases, such as wound healing, tumorigenesis, and cancer development (2, 3). AMBN (ameloblastin), also known as amelin and sheathlin, is a tooth-specific extracellular matrix and the most abundant non-amelogenin enamel matrix protein (4 -6). AMBN is expressed primarily by ameloblasts, which are differentiated from the oral ectoderm and form a polarized single cell layer underlying the enamel matrix. In a previous study, we created Ambn-null mice and demonstrated that AMBN is required for cell attachment and polarization and for maintaining the differentiation state of ameloblasts and is essential for enamel formation (3). Overexpression of Ambn in transgenic mice causes abnormal enamel crystallite formation and enamel rod morphology (7). These results suggest that enamel formation and rod morphology are influenced by temporal and spatial expressions of AMBN and imply that the AMBN gene locus may be involved in the etiology of a number of cases of undiagnosed hereditary amelogenesis imperfecta (8). Further, it was reported that recombinant AMBN enhances pulpal wound healing and reparative dentine formation following pulpotomy procedures, suggesting that it functions as a signal molecule in epithelial-mesenchymal interactions (9).We previously reported that about 20% of Ambn-null mice developed an odontogenic tumor of dental ep...

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“…It was previously reported that local applications of bioactive molecules such as bone morphogenetic proteins (BMPs) (5,6) and recombinant fusion ameloblastin (7) to pulp exposure induced appropriate reparative dentin formation. However, there are few studies regarding vital pulp therapy to form new dentin in defects and regenerate the dentin-pulp complex (8,9).…”

mentioning

confidence: 99%

Formation of Dentin-like Particles in Dentin Defects above Exposed Pulp by Controlled Release of Fibroblast Growth Factor 2 from Gelatin Hydrogels

Kikuchi

Kitamura

Morotomi

et al. 2007

Journal of Endodontics

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Ameloblastin Fusion Protein Enhances Pulpal Healing and Dentin Formation in Porcine Teeth

Cited by 27 publications

References 20 publications

Whole exome sequencing identifies an AMBN missense mutation causing severe autosomal-dominant amelogenesis imperfecta and dentin disorders

Whole exome sequencing identifies an AMBN missense mutation causing severe autosomal-dominant amelogenesis imperfecta and dentin disorders

Critical Role of Heparin Binding Domains of Ameloblastin for Dental Epithelium Cell Adhesion and Ameloblastoma Proliferation

Formation of Dentin-like Particles in Dentin Defects above Exposed Pulp by Controlled Release of Fibroblast Growth Factor 2 from Gelatin Hydrogels

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