Study Shows Molecular Events that Contribute to Its
For immediate release: July 3, 2003
Contact: Mary Daum
(301) 594-7559, Mary.Daum@nih.gov
A team led by scientists at the National Institute of Dental and Craniofacial
Research (NIDCR) 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 (DSPP) 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 (DGI-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
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.
Collaborating with Drs. Kulkarni and Sreenath were NIDCR’s Tamizchelvi
Thyagarajan, Bradford Hall, and Glenn Longenecker; Rena D’Souza from the
University of Texas Health Science Center at Houston; Sung Hong and J. Tim
Wright from the University of North Carolina, Chapel Hill; Mary MacDougall, from
the University of Texas Health Science Center at San Antonio; and John Sauk from
the University of Maryland at Baltimore.
The NIDCR is one of the National Institutes of Health in Bethesda, Md. NIH
is an agency of the U.S. Department of Health and Human