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Amelogenesis and Ameloblast Life Cycle

Amelogenesis is the process of formation of enamel and this enamel formation is done by Ameloblasts. These ameloblasts are actually the Inner enamel epithelium of the enamel organ, which are called ameloblasts only when they are fully differentiated. So life cycle of Ameloblasts are the functional stages of the cells of the Inner enamel epithelium which they pass through during tooth development and eruption. The life cycle has 6 stages. Morphogenic stage, Organizing stage, Formative stage, Maturative stage, Protective stage and Desmolytic stage. These stages are sometimes classified under 3 categories. Pre-secretary stage in which the cells prepare themselves for secreting enamel. Secretory stage in which the actual enamel formation occurs and Post-Secretary state in which maturation and protection of enamel is done. For descriptive purpose, the side of the Ameloblasts towards Stratum intermedium is the proximal end and the side towards the dental papilla, where enamel is formed is the distal end. Morphogenic stage. The cells of the Inner enamel epithelium decide the morphology of the crown of the tooth that is to be formed. Hence, the name morphogenic stage. In this stage, the cells of the Inner enamel epithelium are short columnar with a large oval nuclei which fills the cell body. The mitochondria are evenly distributed in the cytoplasm, whereas the golgi bodies and centrioles are located in the proximal end. A basement membrane is attached to these cells which separates them from the connective tissue of the dental papilla. There is a 'cell free zone' just beneath the inner enamel epithelium in the dental papilla which has no cells. Organizing stage. In this stage the Inner enamel epithelium cells organize themselves to differentiate into Ameloblast, hence the name Organizing stage. The cells increase in size and become tall columnar. The nucleus shifts towards the proximal end, this shift is called the 'reversal of polarity', which creates a 'nucleus free zone' in the distal half of the Ameloblasts. The mitochondria shift towards the proximal end, whereas golgi bodies and centrioles move to the distal end. The basement membrane is still present, whereas the 'cell free zone' of the Dental papilla disappears, as the Ameloblasts elongate and come in direct contact with the cells of the Dental papilla, so to differentiate them to Odontoblasts. Formative stage. Once cells of the Dental papilla differentiate into Odontoblast they start depositing Dentin. This dentin sends signal to the Ameloblast to form Enamel, hence entering the Formative stage, and the Enamel organ enters the Advanced Bell Stage. The Ameloblasts elongate and develop pyramidal processes at the distal end called 'Tomes process'. The Tomes processes are separated from the cell proper by an incomplete septa called 'distal terminal bars'. Basement membrane disintegrates in this stage. Coming to the Tomes process, they have a Non-secretory side and a Secretory side. The Secretory side has again two parts, proximal part and a distal part. The distal part produces the enamel rod and the proximal part produces the inter-rod. The inter-rod formation is always a step ahead of the rod formation. Apart from these changes Ameloblasts also undergo the 'reversal of nutrition'. That is, till the Organizing stage, the Ameloblasts were getting nutrition from the Dental papilla, but once Formative stage begins and Enamel, Dentin deposition starts, this source of nutrition gets blocked. The new source of nutrition is the dental sac adjacent to the Outer enamel epithelium. Maturative stage. Once the whole thickness of Enamel is formed, then Ameloblasts enter the Maturative stage. In Maturative stage, two processes take place. First, the organic matter is reabsorbed from the enamel. Second, minerals are released into it. Hence, maturation of enamel occurs. About 50% of Ameloblasts undergo degeneration by apoptosis. In the Ameloblasts, Tomes processes disappear, the cells reduce in size but are still tall columnar. They re-secrete the basement membrane between them and the enamel. The distal surface of the Ameloblasts now alternates between being smooth and ruffled. When cells have a ruffled border, they are relatively in a more active state. The Ameloblasts have numerous lysosomes, shows endocytosis of enamel organic matrix and simultaneously pump out calcium for mineralization. They also release bicarbonates to maintain the pH. Whereas, when Ameloblasts have a smooth border, they are relatively less active and only absorb some enamel proteins. This process by which Ameloblasts alternate cyclically between having ruffled border and smooth border is called 'modulation' and it occurs every 6-8 hours. The Maturative stage is about 3 times longer than the Formative stage. Protective stage. Once whole enamel is formed and mineralized, the function of Ameloblasts is over. Now this Enamel needs to be protected. From what? From the surrounding connective tissue. If this enamel comes in contact with the connective tissue, two things may happen, either resorption of the enamel and formation of developmental anomalies, or it may cause deposition of cementum. So this protective role is played by the Ameloblasts, as they are already covering the Enamel. The Ameloblasts from being tall columnar cells reduce in size and become cuboidal and cannot be distinguished from the other layers. The Enamel organ itself is reduced in size and is now called Reduced Enamel Epithelium. Desmolytic stage. In addition to protecting the formed enamel, the reduced enamel epithelium releases enzymes into the surrounding connective tissue. These enzymes cause desmolysis, hence the Desmolytic stage, and therefore helps in eruptive movements of the tooth. That is why, premature loss of reduced enamel epithelium may prevent the eruptive movement of the tooth.