Dental Disorder
Human Dental Disorder Mouse Created That Mimics Human Dental Problems
 

Human Dental Disorder Mouse Created That Mimics Human Dental Problems

A team led by scientists at the National Institute of Dental and Craniofacial Research has created a mouse model with tooth defects similar to those of people with dentinogenesis imperfecta III. The model will allow scientists to learn more about how the hereditary disorder arises and provides a tool for developing and testing treatments. The researchers report their findings in the July 4 issue of the Journal of Biological Chemistry.

Dr. Ashok Kulkarni and his colleagues created the mouse model by deleting or 'knocking out' the dentin sialophosphoprotein gene, thought to be responsible for coordinating the mineralization of a tooth's dentin. The animals' teeth showed discoloration, large pulp cavities, and pulp exposure. Detailed studies of the teeth revealed abnormalities in the dentin. Dentin is a hard material similar to bone that makes up about three-fourths of an adult tooth. It lies between the outer enamel and the innermost core of the tooth called the dental pulp.

Our study shows that DSPP plays a key role in orchestrating the process of dentin mineralization, or maturation, said senior author Dr. Kulkarni from the NIDCR Functional Genomics Unit and Gene Targeting Facility. This mouse model shows for the first time some of the molecular events regulated by DSPP that are involved in dentin mineralization. For example, we found that DSPP probably regulates two proteoglycans, or proteins, during this process, something we didn't expect to find. Dentin formation requires several steps: First, dentin-forming cells secrete the proteins that make up dentin's scaffolding. Mineralization occurs as dentin hardens when calcium is deposited onto this framework. The areas that are first to mineralize grow and then fuse to create one calcified mass that is the mature dentin.

Dentinogenesis imperfecta, classified into three subtypes, occurs in about 1 in 8,000 newborns in the U.S. The teeth can be bluish or brownish with a somewhat translucent appearance. On x-ray, the teeth of patients with dentinogenesis imperfecta III appear as 'shell teeth,' with a layer of enamel, a thin layer of dentin, and very large pulp chambers. Because of the unstable dentin, the enamel can shear off and expose the dentin, which could then wear down to the pulp. Most of those severely affected with DGI-III are candidates for dentures or implants by age 30 despite dental intervention.

In-depth studies of the DGI-III animal teeth revealed an abnormally large area of unmineralized dentin, or predentin, and an irregular border between the predentin and its mature counterpart. Additionally, there was evidence of partially mature dentin trapped between areas that were fully mineralized. In a normal tooth, the mature dentin would be mineralized completely, the scientists said.

Other studies found unusually large amounts of two proteoglycans called decorin and biglycan within the unmineralized areas. The theory is that these two proteoglycans help promote mineralization, said Dr. Taduru Sreenath, the study's first author. But without DSPP to give the correct instructions, these proteins are too active and, in fact, interfere with the process. Dr. Sreenath explained that in normal dentin, decorin and biglycan are probably degraded and then mineralization proceeds.

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Author Notes:

James Wilkinson contributes and publishes news editorial to http://www.teeth-whitening-smiles.com.  Everything you need to know to get a whiter, brighter smile!

 
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