Biomedical subjects

J Tim Wright

Publications and source records attributed to J Tim Wright.

6 recordsLinked to original sources

PubMed2006

Overexpression of transforming growth factor-beta1 in teeth results in detachment of ameloblasts and enamel defects.

Transforming growth factor-beta1 (TGF-beta1) is a key regulator of many cellular processes, including cell adhesion, the immune response and synthesis of extracellular matrix proteins. In the present study, we report the characterization of enamel defects in a transgenic mouse model overexpressing TGF-beta1 in odontoblasts and ameloblasts, its expression being driven by the promoter sequences of the dentin sialophosphoprotein gene. As reported earlier, these mice develop distinct dentin defects similar to those seen in human dentin dysplasia and dentinogenesis imperfecta. A further detailed examination of enamel in these mice revealed that from the early secretory stage, ameloblasts began to detach from dentin to form cyst-like structures. A soft X-ray analysis revealed that this cyst-like structure had a disorganized and partially mineralized matrix with an abnormal mineralization pattern and a globular appearance. In the molars, the enamel was not only pitted and hypoplastic, but enamel rods were completely lost. Thus, altered TGF-beta1 expression in the tooth seems to trigger detachment of ameloblasts and abnormal secretion and deposition of minerals in the cyst-like structures adjoining the dentin. We speculate that the altered expression of TGF-beta1 in teeth impacts the adhesion process of ameloblasts to dentin.

Ameloblasts↗

PubMed2006

Human enamel phenotype associated with amelogenesis imperfecta and a kallikrein-4 (g.2142G>A) proteinase mutation.

Kallikrein-4 is known to be highly expressed during the maturation stage of enamel formation and is thought to be critical for the final phase of crystallite growth. The purpose of this study was to evaluate the enamel phenotype in humans with a known KLK-4 mutation (g.2142G>A). Primary teeth from two individuals with a known KLK-4 mutation were evaluated using amino acid analysis and light and electron microscopy. Light microscopy showed the enamel was of normal thickness but opaque throughout its width compared with normal enamel. Electron microscopy showed enamel affected by the KLK-4 mutation had a normal prismatic structure and generally had a well-organized and discernable crystallite composition. In some areas, globular structures were present where crystallites were not discernable or appeared to have an altered morphology. The KLK-4 mutant enamel had an increased protein content compared with normal enamel. Human enamel formed with a lack of functioning KLK-4 proteinase is altered primarily in the completeness of crystallite growth, while enamel thickness and prism structure remains essentially normal. Collectively, these studies suggest that the KLK-4 proteinase is essential for the final crystallite growth of enamel but is not critical for crystallite orientation, prism formation or enamel thickness.

Adenine↗

PubMed2005

Variation in dental and skeletal open bite malocclusion in humans with amelogenesis imperfecta.

The amelogenesis imperfectas (AI) are a diverse group of genetic disorders primarily affecting the quality and or quantity of enamel, however, affected individuals often have an open bite malocclusion. Three main AI types are recognized based on the perceived developmental mechanisms involved and the enamel phenotype. The purpose of this investigation was to evaluate the association of the AI enamel defect with craniofacial features characteristic of an open bite malocclusion. The sample consisted of 54 AI affected and 34 unaffected family members from 18 different kindreds. Lateral cephalograms were digitized and measurements evaluated for vertical plane alterations using Z-scores. Forty two percent of AI affected individuals and 12% of unaffected family members had dental or skeletal open bite malocclusions. Skeletal open bite malocclusion was variably expressed in AI affected individuals. The enamel phenotype severity did not necessarily correspond with the presence or severity of open bite malocclussion. Open bite malocclusion occurred in individuals with AI caused by mutations in the AMELX and ENAM genes even though these genes are considered to be predominantly or exclusively expressed in teeth. Affected AI individuals with cephalometric values meeting our criteria of skeletal open bite malocclusion were observed in all three major AI types. The pathophysiological relationship between AI associated enamel defects and open bite malocclusion remains unknown.

Adolescent↗

PubMed2003

The receptor activator of nuclear factor-kappa B ligand-mediated osteoclastogenic pathway is elevated in amelogenin-null mice.

Amelogenins, major components of developing enamel, are predominantly involved in the formation of tooth enamel. Although amelogenins are also implicated in cementogenesis, their precise spatial expression pattern and molecular role are not clearly understood. Here, we report for the first time the expression of two alternate splice forms of amelogenins, M180 and the leucine-rich amelogenin peptide (LRAP), in the periodontal region of mouse tooth roots. Lack of M180 and LRAP mRNA expression correlated with cementum defects observed in the amelogenin-null mice. The cementum defects were characterized by an increased presence of multinucleated cells, osteoclasts, and cementicles. These defects were associated with an increased expression of the receptor activator of the nuclear factor-kappa B ligand (RANKL), a critical regulator of osteoclastogenesis. These findings indicate that the amelogenin splice variants, M180 and LRAP, are critical in preventing abnormal resorption of cementum.

Alternative Splicing↗

PubMed2003

Dentin sialophosphoprotein knockout mouse teeth display widened predentin zone and develop defective dentin mineralization similar to human dentinogenesis imperfecta type III.

Dentin sialophosphoprotein (Dspp) is mainly expressed in teeth by the odontoblasts and preameloblasts. The Dspp mRNA is translated into a single protein, Dspp, and cleaved into two peptides, dentin sialoprotein and dentin phosphoprotein, that are localized within the dentin matrix. Recently, mutations in this gene were identified in human dentinogenesis imperfecta II (Online Mendelian Inheritance in Man (OMIM) accession number 125490) and in dentin dysplasia II (OMIM accession number 125420) syndromes. Herein, we report the generation of Dspp-null mice that develop tooth defects similar to human dentinogenesis imperfecta III with enlarged pulp chambers, increased width of predentin zone, hypomineralization, and pulp exposure. Electron microscopy revealed an irregular mineralization front and a lack of calcospherites coalescence in the dentin. Interestingly, the levels of biglycan and decorin, small leucine-rich proteoglycans, were increased in the widened predentin zone and in void spaces among the calcospherites in the dentin of null teeth. These enhanced levels correlate well with the defective regions in mineralization and further indicate that these molecules may adversely affect the dentin mineralization process by interfering with coalescence of calcospherites. Overall, our results identify a crucial role for Dspp in orchestrating the events essential during dentin mineralization, including potential regulation of proteoglycan levels.

Animals↗

PubMedDate not supplied

Quantitative assessment of enamel hypomineralization by KaVo DIAGNOdent at different sites on first permanent molars of children in China.

PURPOSE: The purpose of this study was to identify the most caries-susceptible site of pits and fissures on first permanent molars by quantitative evaluation of the mineralization in both caries-active and caries-free children, and to provide helpful information for cost-effective, targeted prevention. METHODS: Eighty-four caries-free and 85 caries-active children were selected from 800 6- to 7-year-old children with fully erupted first permanent molars. Hypomineralization of the central fossa (CF) and lingual pit (LP) of the maxillary or buccal pit (BP) of mandibular first permanent molars were evaluated by KaVo DIAGNOdent. Statistical analysis included grouped t test and single-factor variance analysis and paired comparison. RESULTS: CF of mandibular first permanent molars had significantly greater hypomineralization than other sites. The hypomineralization of the maxillary CF is more severe than that of LP. The extent of the hypomineralization of each site at the first permanent molar in caries-active children was significantly higher than that in caries-free children. CONCLUSIONS: Central fossae of first mandibular molars are the most hypomineralized sites in both caries-free and caries-active groups. The results suggest that preventive interventions should be targeted at the CF of mandibular molars with special concern given to the caries-active population.

Analysis of Variance↗