Dentistry and Medical Research

: 2021  |  Volume : 9  |  Issue : 1  |  Page : 5--8

Ameloblasts in health and disease

Sandhya Tamgadge1, Avinash Tamgadge1, Bhagyashree Agre2,  
1 Department of Oral and Maxillofacial Pathology and Microbiology, D Y Patil University School of Dentistry, Navi, Mumbai, Maharashtra, India
2 Department of Oral and Maxillofacial Pathology and Microbiology, Bharti Vidyapeeth Dental College and Hospital, Navi, Mumbai, Maharashtra, India

Correspondence Address:
Sandhya Tamgadge
Department of Oral and Maxillofacial Pathology and Microbiology, D. Y Patil University School of Dentistry, Nerul, Navi Mumbai - 400 706, Maharashtra


Ameloblasts are highly sensitive enamel-forming cells. They are derived from ectoderm and undergo a series of transformative changes in their life cycle. The functional efficiency of ameloblasts depends on various factors such as intracellular and extracellular environment, epithelial–mesenchymal interactions, and genetic control. Enamel formation is a well-organized event in the life cycle of ameloblasts. Normal enamel formation is the sign of healthy ameloblasts. The well-being of ameloblasts would be under threat in multiple situations. Internal regulatory mechanisms that are influenced by genetic mutations will lead to abnormal behavior of the cell. Environmental factors such as trauma, infection, exposure to chemicals, nutritional deficiencies, and hormonal dysregulation would affect the cell's normal behavior, which leads to abnormal enamel production. In this article, factors affecting the health of ameloblasts are described briefly.

How to cite this article:
Tamgadge S, Tamgadge A, Agre B. Ameloblasts in health and disease.Dent Med Res 2021;9:5-8

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Tamgadge S, Tamgadge A, Agre B. Ameloblasts in health and disease. Dent Med Res [serial online] 2021 [cited 2021 Dec 4 ];9:5-8
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Ameloblasts are cells that form the hardest tissue of the body, the enamel. These cells can give rise to multiple diseases such as developmental disorders, neoplasm, and cysts, when faced with inappropriate stimuli.[1] Hence, this review article briefly describes the ameloblasts in health and disease.

 Ameloblasts in Health

Developmental aspect of ameloblasts

Ameloblasts are responsible for enamel formation in the teeth. They are derived from preameloblasts. Preameloblasts are the derivatives of neural crest cells. Neural crest cells are generated from ectoderm. There are three germ layers from which all tissues of the body are formed. These germ layers are namely ectoderm, mesoderm, and endoderm.[1]

Ameloblasts exist in the human body from the beginning of enamel formation till its completion. After completion of enamel formation, they become part of reduced enamel epithelium, which forms the primary attachment epithelium as the tooth erupts in the oral cavity[2] [Figure 1]. After which, ameloblasts no longer exist in the body. Therefore, enamel cannot be repaired or regenerated.{Figure 1}

Tooth development begins during the 6th week of intrauterine life when the first sign of tooth development is seen. Various stages of tooth development are bud stage, cap stage, bell stage, and advanced bell stage. This tooth-forming apparatus is called the enamel organ.[1]

In the bell and advance bell stage, the enamel organ becomes distinct. It assumes a shape of a bell. The outer aspect of a bell stage shows outer enamel epithelium or external dental epithelium. The inner aspect of a bell is lined by cells of inner enamel epithelium. The meeting point of the inner and outer enamel epithelium is called as the cervical loop. It is the cells of inner enamel epithelium that becomes preameloblasts in bell stage and becomes ameloblasts in advance bell stage.[2]

Ameloblasts and matrix deposition

Secretory ameloblasts (SABs) are tall, columnar, and polarized cells.[3]

SABs involve growth and elongation of the cytoplasm, a change in polarity, and sequential development of organelles. The undifferentiated cells of the ameloblastic layer initially produce material for internal use. As soon as enamel matrix begins to be deposited at the distal surface, ameloblasts recede, leaving the cytoplasmic extension (Tomes process) in the early calcifying enamel.[1],[2],[4],[4]

Amelogenesis is the formation of enamel by ameloblasts. The major proteins secreted by ameloblasts are amelogenins, enamelins, ameloblastins, and tuftelins that are produced by the ameloblasts into the extracellular space. Ameloblastin simultaneously halts proliferation of ameloblasts, whereas enamelins and amelogenins are essential for the deposition of hydroxyapatite crystals. Ameloblastins and amelogenins are removed during maturation when ameloblasts produce proteinases (e.g., MMP), cleaving these substances. The debris is consumed by ameloblasts, and the enamel turns into an extremely mineralized tissue. Half of the ameloblasts undergo apoptosis during amelogenesis; the rest die after the process ends. Therefore, amelogenesis stops at the point of tooth eruption, and there is no production of secondary or regenerative enamel.[6]

Intracellular control and extracellular control in ameloblasts–Preameloblasts differentiation into SABs rely on a highly regulated network of interactions between conserved signal transduction pathways, including members of the bone morphogenetic protein transforming growth factor-beta, Notch, and mitogen-activated protein kinase (MAPK) pathways to coordinate all aspects of ameloblasts in intracellular processes and their social contexts.[3]

 Ameloblasts in Disease

The enamel phenotype resulting from different types of injuries during amelogenesis will vary depending on the type of stress as well as duration and intensity of the influence.[7]

Environmental stressors of short span (e.g., fever) often cause localized deformities, whereas chronic stressors (e.g., elevated fluoride exposure) are more likely to be associated with generalized defects.[8]

Genetic disorders of ameloblasts

There are several classes of genes in ameloblasts life cycle elucidating the molecular regulatory cascades.

Junctional epidermolysis bullosa

It is due to weakness in the cell-to-cell adhesion. The abnormal proteins from defective genes result in fragile skin that blisters. Interestingly, some mutations in genes such as laminin subunit beta 3 can result only as enamel hypoplasia (enamel phenotype).[9]

Tricho-dento-osseous syndrome

It is related to kinky curly hair at birth, dense-thick bone, generalized thin and/or pitted enamel, and large pulp chambers.[10]

Mutations in the p63 gene, an essential gene in cell growth, causes a variety of ectodermal dysplasia (ED) syndromes (e.g., Rapp Hodkins syndrome, ectrodactyly, ED cleft syndrome), all of which can have enamel defects.[11]

Kohlschütter-Tönz syndrome

This syndrome has a distinct phenotype where all teeth exhibit a yellow-brown discoloration of the enamel and a decreased level of mineralization. The ROGDI gene (Rogdi Atypical Leucine Zipper) was not known to be critical for enamel formation before this discovery.[12],[13]

Jalili syndrome

Affected individuals have cone-rod dystrophy in the eyes and enamel that has a brown appearance and is hypomineralized. This condition is caused by mutations in the cyclin and domain cystathionine β-synthase (CBS) divalent metal transport mediator 4 gene (CNNM4) (cyclin and CBS domain divalent metal cation transport mediator 4) that may play a role in metal-ion transport.[14]

Cystic fibrosis (CF)

It is caused by mutations in the CFTR gene (CF transmembrane conductance regulator) that is involved in regulating ion movement and pH regulation. Clinical evaluation of humans with CF found a high percentage of affected individuals had associated enamel defects of varying severity.[15]

Amelogenesis imperfecta

Hereditary nonsyndromic conditions primarily affecting the enamel are referred to as amelogenesis imperfecta (AI). Enamel mineralization relies on Ca2+ availability provided by Ca2+ release-activated by Ca2+ (CRAC) channels. CRAC channels are modulated by the endoplasmic reticulum Ca2+ sensor stromal interaction molecule 1 (STIM1) which gates the pore subunit of the channel known as ORAI calcium release-activated calcium modulator 1 (ORAI1) found in the plasma membrane, to enable sustained Ca2+ influx. Mutations in the STIM1 and ORAI1 genes result in CRAC channelopathy, an ensemble of diseases including immunodeficiency, muscular hypotonia, ED with defects in sweat gland function, and abnormal enamel mineralization similar to AI.[12]

Hereditary ectodermal dysplasia

Patients with mutations in STIM1 and ORAI1 have been described as presenting with ED, similar to those in ED patients.[12]

Enamel hypoplasia

Enamel hypoplasia may develop on the tooth due to instabilities during secretory stage of amelogenesis. Injuries during later stages of enamel formation, calcification, and maturation may result in enamel opacities.[8]

Variability in the development of the defects is caused by selective involvement of only those ameloblasts active at the time of disturbance. Some of the affected ameloblasts die and discontinue secreting enamel matrix, while other cells continue to secrete normal enamel over the defective areas.[16]

Enamel hypoplasia is associated with Usher syndrome, Ellis Van Creveld syndrome, fluorosis, fever, starvation, excess fluoride exposure, trauma, hypoxia infection, tetracyclines, low birth weight, and hyperbilirubinemia.[8]

 Nonhereditary Disorders of Ameloblasts

Odontogenic tumors


Ameloblastoma is a slow-growing, locally invasive, benign epithelial odontogenic neoplasm. It is thought to arise from SOX2-expressing dental lamina epithelium and remnants of the tooth-forming enamel organ. The tumor exhibits proliferation of epithelial cells resembling preameloblasts on a basement membrane.[8]

Ameloblastic fibroma

Ameloblastic fibroma is a tumor of odontogenic origin characterized by the proliferation of both epithelial and mesenchymal odontogenic tissues without the formation of hard tissue structures.[1] The epithelial (ameloblastic) component consists of islands and cords of odontogenic epithelium that often resembles the dental lamina of early tooth development. There is usually sufficient differentiation of the peripheral cells of these islands, and characteristic high cuboidal or columnar ameloblasts can be recognized.

The islands often show a peripheral row of high cuboidal or columnar, ameloblasts-like cells.[17]

Malignant ameloblastoma

The terms malignant ameloblastoma and ameloblastic carcinoma have been used interchangeably for these variants in the past. Malignant ameloblastoma and ameloblastic carcinoma are two distinct types of ameloblastoma. Ameloblastic carcinoma is locally aggressive and may or may not undergo regional lymph node metastasis, whereas malignant ameloblastoma would show metastasis.[18],[19]


Tooth-like structures with central cores of the pulp tissue are seen microscopically. They consist of haphazardly encased pulp in dentin shells and partially covered by conglomerates of dentin, enamel, enamel matrix, enamel surrounded by a fibrous capsule similar to the cementum, and pulp tissue follicle surrounding a normal tooth.[20]

The etiology of odontomas is believed to have its origin from mature ameloblasts. These specialized cells have the potential of developing tumors with a wide variation in appearance and content.

Odontomas, by definition alone, refer to any tumor of odontogenic origin. Odontomas result from the growth of completely differentiated epithelial and mesenchymal cells that give rise to ameloblasts and odontoblasts.[5] In a broad sense, it means growth with both the epithelial and mesenchymal components exhibiting complete differentiation resulting in functional ameloblasts and odontoblasts.[5] These cells in turn form variable amounts of enamel and dentin and pulpal tissue of the odontoma.[7] These enamel and dentin were usually laid down in an abnormal pattern because the organization of odontogenic cells failed to reach the normal state of morpho-differentiation.[5] Hence, they are considered as developmental anomalies rather than true neoplasm.[18],[21]

 Odontogenic Cysts

Dentigerous cysts

The pathogenesis of dentigerous cysts is indistinct. It is proposed that dentigerous cysts develop from abnormal fluid accumulation between the reduced enamel epithelium and the enamel or within the enamel organ. The proliferation of the epithelium may be induced by osmotic pressure from the fluid-filled sac when the tooth is impacted.[22]

Eruption cysts

It is a soft tissue analog of the dentigerous cyst.[22]

Ethical clearance

Ethical document wasn't considered as it is not a research based article having patients clinical data.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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