Accelerated enamel mineralization in Dspp mutant mice

Abstract

Dentin sialophosphoprotein (DSPP) is one of the major non-collagenous proteins present in dentin, cementum and alveolar bone; it is also transiently expressed by ameloblasts. In humans many mutations have been found in DSPP and are associated with two autosomal-dominant genetic diseases — dentinogenesis imperfecta II (DGI-II) and dentin dysplasia (DD). Both disorders result in the development of hypomineralized and mechanically compromised teeth. The erupted mature molars of Dspp–/– mice have a severe hypomineralized dentin phenotype. Since dentin and enamel formations are interdependent, we decided to investigate the process of enamel onset mineralization in young Dspp–/– animals. We focused our analysis on the constantly erupting mouse incisor, to capture all of the stages of odontogenesis in one tooth, and the unerupted first molars. Using high-resolution microCT, we revealed that the onset of enamel matrix deposition occurs closer to the cervical loop and both secretion and maturation of enamel are accelerated in Dspp–/– incisors compared to the Dspp+/– control. Importantly, these differences did not translate into major phenotypic differences in mature enamel in terms of the structural organization, mineral density or hardness. The only observable difference was the reduction in thickness of the outer enamel layer, while the total enamel thickness remained unchanged. We also observed a compromised dentin-enamel junction, leading to delamination between the dentin and enamel layers. The odontoblast processes were widened and lacked branching near the DEJ. Finally, for the first time we demonstrate expression of Dspp mRNA in secretory ameloblasts. In summary, our data show that DSPP is important for normal mineralization of both dentin and enamel.

Haploinsufficiency of Dspp Gene Causes Dentin Dysplasia Type II in Mice

“…To the best of our knowledge, our report was the first to claim the haploinsufficiency of Dspp gene in mice and a DD-II-like mouse model. Our findings were contrary to the publications, which addressed no dental phenotypes in the Dspp heterozygous mice (Suzuki et al, 2009;Verdelis et al, 2016;Zhang et al, 2018). However, the heterozygous mice used in their studies were younger than 6 months old.…”

“…Our findings were contrary to the publications, which addressed no dental phenotypes in the Dspp heterozygous mice ( Suzuki et al, 2009 ; Verdelis et al, 2016 ; Zhang et al, 2018 ). However, the heterozygous mice used in their studies were younger than 6 months old.…”

“…We also found the DGI-III-like phenotypes in Dspp knockout mice at the ages of 3 and 6 months ( Gibson et al, 2013a ). Besides, we and others found that Dspp knockout mice also developed periodontal defects ( Gibson et al, 2013b , 2014 ), as well as accelerated secretion and maturation of enamel ( Verdelis et al, 2016 ). However, Dspp heterozygous mice did not show any abnormalities, and the authors suggested that haploinsufficiency did not play a role in these mice ( Suzuki et al, 2009 ).…”

Mutation inSSUH2Causes Autosomal-Dominant Dentin Dysplasia Type I

“…Moreover, the DSPP mutation in mice resulted in accelerated enamel mineralization, but similar tooth phenotypes were absent from humans. This indicates that the mechanisms governing, and mediators involved in, odontogenesis in mice differ from those involved in odontogenesis in humans [Verdelis et al., ]. In future work, a knockout mouse model will be used to determine the exact role of SSUH2 in odontogenesis.…”

3D MicroCT spatial and temporal characterization of thoracic aorta perivascular adipose tissue and plaque volumes in the ApoE-/- mouse model

“…We found greater volumes of descending thoracic aorta PVAT associated with CVD measures 10 Indeed there is intense clinical interest to develop quantitative measures implicated in CVD progression or CV events, which has led some to focus on the PVAT and, in particular, various measures derived from clinical CT scans including thresholding techniques and attenuation indices [10][11][12] The goal of this study was to develop a technical protocol beginning with CONTACT Kelly J. Shields kelly.shields@ahn.org Allegheny Health Network, Allegheny General Hospital, 320 E North Avenue, 8 th Floor South Tower, Pittsburgh, PA 15212, USA appropriate soft tissue labeling through to imaging with high resolution 3D micro-computed tomography (microCT) in order to dramatically improve the ability to evaluate animal models of cardiovascular disease. This novel imaging technique is typically used for hard biological tissue, [13][14][15] however, we are using the technique to characterize the temporal and spatial development of 1) aorta vascular wall volumea surrogate measure of vascular remodeling, 2) aorta PVAT volume and 3) luminal plaque volume in a robust atherosclerotic mouse model [16][17][18][19][20]…”