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Genetic evidences for future dental treatments: forming enamel
26 February 2009
Zurich, University of
A team of researchers lead by Professor Dr Thimios Mitsiadis at the University of Zurich, Switzerland, has identified a gene responsible for the formation of enamel, which is the key component of the teeth. The experiments were accomplished in mice carrying a deletion of the transcription factor Tbx1, a gene that plays a principal role in several human malformations (heart, thymus, parathyroid, face, and teeth) associated to the DiGeorge syndrome.
«Subjects afflicted by DiGeorge syndrome exhibit teeth with enamel defects. We have demonstrated that a direct link between impaired Tbx1 function and enamel defects exists. Enamel forms via the mineralization of specific enamel proteins that are secreted by dental epithelial cells called ameloblasts. Our results clearly show that teeth of Tbx1 null mice lacked enamel and ameloblasts» explains Prof Mitsiadis.
These findings, just published in Development Biology, represent a major contribution to the understanding of the production of enamel, the «hardest organic tissue» found in nature.
An American group of researchers from the University of Oregon have also shown a relationship between another transcription factor (Ctip2) and the production of enamel, but in the words of Prof Mitsiadis «our investigations better demonstrate the lack of enamel in teeth. Because of the early lethality of the Tbx1 mutant mice, we have used long-term culture techniques that allow the unharmed growth of teeth until their full maturity. No such studies were performed from our American colleagues».
Could dental treatment benefit in the future from this revolutionary study? The answer is definitively yes. «The understanding of the genetic code controlling tooth development and repair will permit us to imagine and generate new products and replacement tissues for injured and unhealthy teeth. However the requirements for functional tooth repair and/or formation are complex. Yet, a single approach has not allowed an effective clinical therapy» says Prof Mitsiadis.
Is it possible to use dental stem cells to stimulate the growth of new enamel? This represents the biggest challenge in the discipline of tooth engineering. «Our results show that Tbx1 is involved in the maintenance of dental epithelial stem cells that are responsible for ameloblast formation. In some cases of genetic tooth anomalies, regeneration and repair of teeth could be treated by stem cells. Aggregates of dental stem cells could be used in the future for local transplantation in the dental tissues» explains Prof Mitsiadis
A normal mature mouse incisor is shown on the left, where ameloblasts (am) that produce enamel (e) is clearly visible. On the right is a mature incisor with the Tbx1 gene deleted, and no enamel and ameloblasts were able to form.