Rare Bone Diseases and Their Dental, Oral, and Craniofacial Manifestations

Foster, BL; Ramnitz, Mary Scott; Gafni, Rachel I; Burke, Andrea B.; Boyce, Alison M.; Lee, J.S.; Wright, J. Timothy; Akintoye, Sunday O.; Somerman, M. J.; Collins, Michael T.

doi:10.1177/0022034514529150

Cited by 116 publications

(134 citation statements)

References 63 publications

Supporting

Mentioning

122

Contrasting

Unclassified

Order By: Relevance

“…3A). Similar irregular dentin mineralization has been demonstrated in hypophosphatemic rickets (Opsahl Vital et al 2012;McKee et al 2013;Souza et al 2013;Foster et al 2014). Interestingly, we have recently identified that the overexpression of Trps1 in a preodontoblast-derived cell line results in significant downregulation of Phex and Vdr, whose mutations cause hypophosphatemic rickets (Kuzynski et al 2014).…”

Section: Overexpression Of Trps1 In Secretory Odontoblasts Affects Phsupporting

confidence: 79%

“…Defective dentin is also observed in a genetically heterogeneous group of phosphate homeostasis disorders, such as hypophosphatemic rickets, suggesting the importance of systemic phosphate homeostasis for dentin formation. Hypophosphatemic teeth have enlarged pulp chambers, severely undermineralized dentin, and an irregular mineralization pattern (Souza et al 2010;Opsahl Vital et al 2012;Souza et al 2013;Foster et al 2014). Many of the genes associated with hypophosphatemia are highly expressed by odontoblasts, suggesting that they are involved in dentin mineralization acting locally and independently of systemic phosphate metabolism (Ruchon et al 2000;Bai et al 2002;Thompson et al 2002;Boskey et al 2009).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dspp-independent Effects of Transgenic Trps1 Overexpression on Dentin Formation

et al. 2015

View full text Add to dashboard Cite

The Trps1 transcription factor is highly expressed in dental mesenchyme and preodontoblasts, while in mature, secretory odontoblasts, it is expressed at low levels. Previously, we have shown that high Trps1 levels in mature odontoblasts impair their function in vitro and in vivo. Col1a1-Trps1 transgenic (Trps1-Tg) mice demonstrate defective dentin secretion and mineralization, which are associated with significantly decreased Dspp expression due to direct repression of the Dspp gene by Trps1. Here, by crossing Trps1-Tg and Col1a1-Dspp transgenic (Dspp-Tg) mice, we generated Col1a1-Trps1;Col1a1-Dspp double transgenic (double-Tg) mice in which Dspp was restored in odontoblasts overexpressing Trps1. Comparative micro-computed tomography analyses revealed partial correction of the dentin volume and no improvement of dentin mineralization in double transgenic mice in comparison with Trps1-Tg and wild-type (WT) mice. In addition, dentin of double-Tg mice has an irregular mineralization pattern characteristic for dentin in hypophosphatemic rickets. Consistent with this phenotype, decreased levels of Phex, Vdr, and Fam20c proteins are detected in both Trps1-Tg and doubleTg odontoblasts in comparison with WT and Dspp-Tg odontoblasts. This suggests that the Dspp-independent dentin mineralization defects in Trps1-Tg mice are a result of downregulation of a group of proteins critical for mineral deposition within the dentin matrix. In summary, by demonstrating that Trps1 functions as a repressor of later stages of dentinogenesis, we provide functional significance of the dynamic Trps1 expression pattern during dentinogenesis.

show abstract

Section: Overexpression Of Trps1 In Secretory Odontoblasts Affects Phsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Dspp-independent Effects of Transgenic Trps1 Overexpression on Dentin Formation

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Acellular cementum is essential for anchoring PDL collagen fibers to the root surface. Cementum and bone share regulatory pathways and key developmental influences as evidenced by mouse genetic studies and human disease phenotypes [2–4]. However, accumulated evidence over the past two decades has revealed that acellular cementum is hypersensitive to regulators of mineralization, apparently more so than other hard tissues of the dentition and skeleton [5–7].…”

Section: Introductionmentioning

confidence: 99%

“…HPP causes disturbed skeletal mineralization, including rickets and osteomalacia. In the teeth, HPP appears to disturb dentin and enamel mineralization, but more severely blocks formation and function of acellular cementum in both human subjects and mouse models, leading to PDL detachment and premature tooth loss [2, 10–16]. …”

Section: Introductionmentioning

confidence: 99%

Overlapping functions of bone sialoprotein and pyrophosphate regulators in directing cementogenesis

Chavez

Chu

et al. 2017

Bone

Self Cite

View full text Add to dashboard Cite

Although acellular cementum is essential for tooth attachment, factors directing its development and regeneration remain poorly understood. Inorganic pyrophosphate (PPi), a mineralization inhibitor, is a key regulator of cementum formation: tissue-nonspecific alkaline phosphatase (Alpl/TNAP) null mice (increased PPi) feature deficient cementum, while progressive ankylosis protein (Ank/ANK) null mice (decreased PPi) feature increased cementum. Bone sialoprotein (Bsp/BSP) and osteopontin (Spp1/OPN) are multifunctional extracellular matrix components of cementum proposed to have direct and indirect effects on cell activities and mineralization. Studies on dentoalveolar development of Bsp knockout (Bsp−/−) mice revealed severely reduced acellular cementum, however underlying mechanisms remain unclear. The similarity in defective cementum phenotypes between Bsp−/− mice and Alpl−/− mice (the latter featuring elevated PPi and OPN), prompted us to examine whether BSP is operating by modulating PPi-associated genes. Genetic ablation of Bsp caused a 2-fold increase in circulating PPi, altered mRNA expression of Alpl, Spp1, and Ank, and increased OPN protein in the periodontia. Generation of a Bsp knock-out (KO) cementoblast cell line revealed significantly decreased mineralization capacity, 50% increased PPi in culture media, and increased Spp1 and Ank mRNA expression. While addition of 2 μg/ml recombinant BSP altered Spp1, Ank, and Enpp1 expression in cementoblasts, changes resulting from this dose were not dependent on the integrin-binding RGD motif or by genetic ablation of Ank on the Bsp−/− MAPK/ERK signaling pathway. Decreasing PPi mouse background reestablished cementum formation, allowing more than 3-fold increased acellular cementum volume compared to WT. However, deleting Ank did not fully compensate for the absence of BSP. Bsp−/−;Ank−/− double-deficient mice exhibited mean 20–27% reduced cementum thickness and volume compared to Ank−/− mice. From these data, we conclude that the perturbations in PPi metabolism are not solely driving the cementum pathology in Bsp−/− mice, and that PPi is more potent than BSP as a cementum regulator, as shown by the ability to override loss of BSP by lowering PPi. We propose that BSP and PPi work in concert to direct mineralization in cementum and likely other mineralized tissues.

show abstract

“…XHLR patients require frequent and regular dental care with the main focus on the prevention of attrition due to the fact that the structure of dental hard tissues is severely altered [5,27,34,38,40,46,66]. In the sense of tooth-conserving dentistry bacteria, tight restorations and a preventive sealing should be performed in order to hamper bacterial invasion that may result in pulpitis and further endodontic complications.…”

Section: Resultsmentioning

confidence: 99%

Review of the dental implications of X-linked hypophosphataemic rickets (XLHR)

et al. 2015

View full text Add to dashboard Cite

Objectives The aim of this article was to review the dental implications of X-linked hypophosphataemic rickets (XLHR) and to provide suggestions regarding the dental treatment of these patients. Materials and methods The following search items Bx-linked hypophosphataemia, hypophosphataemic rickets, vitamin Dresistant rickets^were used for literature search. Only full-text articles were analysed and summarized to get an overview of the different treatments and outcomes of hypophosphataemic patients. Results Radiographically, very large pulp chambers with an abnormally high pulp volume/tooth volume ratio, suggesting taurodontism, are often evident. The affected teeth are characterised by a thin enamel layer and dentinal defects. The gender distribution of hypophosphataemic patients is almost equal, but postpubertary males seem to show a trend to develop more severe dental symptoms of the disease. Abscesses without any signs of dental caries or trauma are frequent findings. The most often affected teeth are incisors followed by molars and premolars. Conclusions Treatment options include frequent dental examination, application of topical fluoride varnish and sealing of pits and fissures to prevent microbial invasion that may result in pulpitis and further endodontic complications. Clinical relevance X-linked hypophosphataemic rickets is associated with marked structural alterations of dental hard tissues and the development of multiple abscesses and sinus tracts of dental origin. Therefore, profound knowledge of the various dental implications of XLHR is required to provide these patients with the best possible treatment options.

show abstract

Rare Bone Diseases and Their Dental, Oral, and Craniofacial Manifestations

Cited by 116 publications

References 63 publications

Dspp-independent Effects of Transgenic Trps1 Overexpression on Dentin Formation

Dspp-independent Effects of Transgenic Trps1 Overexpression on Dentin Formation

Overlapping functions of bone sialoprotein and pyrophosphate regulators in directing cementogenesis

Review of the dental implications of X-linked hypophosphataemic rickets (XLHR)

Contact Info

Product

Resources

About