Hypophosphatasia with premature shedding of teeth and aplasia of cementum

Bruckner, Robert J.; Rickles, Norman H.; Porter, Donald R.

doi:10.1016/0030-4220(62)90356-0

Cited by 78 publications

(36 citation statements)

References 15 publications

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“…Compromised periodontal attachment and exfoliation of teeth because of aplasia or severe hypoplasia of acellular cementum is consistently described in case reports and is well documented (5, 7–9, 11, 18–25). Reports on pulp and dentin in cases of HPP are much more variable, with authors frequently citing no observed pathology.…”

Section: Discussionmentioning

confidence: 96%

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Hypophosphatasia-associated Deficiencies in Mineralization and Gene Expression in Cultured Dental Pulp Cells Obtained from Human Teeth

Rodrigues

Foster

Silvério

et al. 2012

Journal of Endodontics

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Introduction Mutations in the gene ALPL in hypophosphatasia (HPP) reduce the function of tissue nonspecific alkaline phosphatase, and the resulting increase in pyrophosphate (PPi) contributes to bone and tooth mineralization defects by inhibiting physiologic calcium-phosphate (Pi) precipitation. Although periodontal phenotypes are well documented, pulp/dentin abnormalities have been suggested in the clinical literature although reports are variable and underlying mechanisms remains unclear. In vitro analyses were used to identify mechanisms involved in HPP-associated pulp/dentin phenotypes. Methods Primary pulp cells cultured from HPP subjects were established to assay alkaline phosphatase (ALP) activity, mineralization, and gene expression compared with cells from healthy controls. Exogenous Pi was provided to the correct Pi/PPi ratio in cell culture. Results HPP cells exhibited significantly reduced ALP activity (by 50%) and mineral nodule formation (by 60%) compared with the controls. The expression of PPi regulatory genes was altered in HPP pulp cells, including reduction in the progressive ankylosis gene (ANKH) and increased ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). Odontoblast marker gene expression was disrupted in HPP cells, including reduced osteopontin (OPN), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), and matrix extracellular phosphoprotein (MEPE). The addition of Pi provided a corrective measure for mineralization and partially rescued the expression of some genes although cells retained altered messenger RNA levels for PPi-associated genes. Conclusions These studies suggest that under HPP conditions pulp cells have the compromised ability to mineralize and feature a disrupted odontoblast profile, providing a first step toward understanding the molecular mechanisms for dentin phenotypes observed in HPP.

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Section: Discussionmentioning

confidence: 96%

“…Dental case reports indicate defective cementum (5, 7, 18, 19), whereas dentin has been described as normal or variably affected (8–11). Here we began to bridge the gap between case reports on dentin pathology and a molecular understanding of how odontoblasts are affected by HPP.…”

Section: Discussionmentioning

confidence: 99%

Hypophosphatasia-associated Deficiencies in Mineralization and Gene Expression in Cultured Dental Pulp Cells Obtained from Human Teeth

Rodrigues

Foster

Silvério

et al. 2012

Journal of Endodontics

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“…27, 28 Dental case reports indicate compromised periodontal attachment and exfoliation of teeth due to aplasia or severe hypoplasia of the acellular cementum. 4, 6, 29, 30 Dentin has been described as normal, or variably affected in HPP, with reports of thin dentin, wide pulp cavities, or “shell teeth.” 9, 10, 31, 32 In studies of Akp2 null mice, a model for human HPP, acellular cementum was inhibited while dentin was reported to be unaffected. 8 The actions of additional extracellular PP i regulators balance and temper TNAP activity.…”

Section: Discussionmentioning

confidence: 99%

Correction of Hypophosphatasia‐Associated Mineralization Deficiencies In Vitro by Phosphate/Pyrophosphate Modulation in Periodontal Ligament Cells

Rodrigues¹,

Foster²,

Silvério³

et al. 2012

Journal of Periodontology

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Background Mutations in the Alpl gene in hypophosphatasia (HPP) reduce the function of tissue nonspecific alkaline phosphatase (TNAP), resulting in increased pyrophosphate (PPi) and a severe deficiency in acellular cementum. We hypothesized that exogenous phosphate (Pi) would rescue the in vitro mineralization capacity of periodontal ligament (PDL) cells harvested from HPP-diagnosed subjects, by correcting Pi/PPi ratio and modulating expression of genes involved with Pi/PPi metabolism. Methods Ex vivo and in vitro analyses were employed to identify mechanisms involved in HPP-associated PDL/tooth root deficiencies. Constitutive expression of PPi-associated genes was contrasted in PDL versus pulp tissues obtained from healthy subjects. Primary PDL cell cultures from HPP subjects (monozygotic twin males) were established to assay alkaline phosphatase activity (ALP), in vitro mineralization, and gene expression. Exogenous Pi was provided to correct Pi/PPi ratio. Results PDL tissues obtained from healthy individuals featured higher basal expression of key PPi regulators, genes Alpl, progressive ankylosis protein (Ankh) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1), versus paired pulp tissues. A novel Alpl mutation was identified in the twin HPP subjects enrolled in this study. Compared to controls, HPP-PDL cells exhibited significantly reduced ALP and mineralizing capacity, which were rescued by addition of 1mM Pi. Dysregulated expression of PPi regulatory genes Alpl, Ankh, and Enpp1 was also corrected by adding Pi, though other matrix markers evaluated in our study remained down-regulated. Conclusions These findings underscore the importance of controlling Pi/PPi ratio toward development of a functional periodontal apparatus, and support Pi/PPi imbalance as the etiology of HPP-associated cementum defects.

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“…Defective cementum formation is seen in hypophosphatasia. Hypophosphatasia can be inherited as an autosomaldominant or -recessive trait (MIM 241500, 241510, 146300) and is characterized by skeletal abnormalities as well as by defective cementum formation (Bruckner et al, 1962). The cementum can be extremely thin and lack sufficient structure for periodontal fiber insertion, resulting in premature tooth loss.…”

Section: Genetic Conditions Affecting Cementummentioning

confidence: 99%

The Impact of Molecular Genetics on Oral Health Paradigms

Hart

Marazita

Wright

2000

Critical Reviews in Oral Biology & Medicine

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As a result of our increased understanding of the human genome, and the functional interrelationships of gene products with each other and with the environment, it is becoming increasingly evident that many human diseases are influenced by heritable alterations in the structure or function of genes. Significant advances in research methods and newly emerging partnerships between private and public sector interests are creating new possibilities for utilization of genetic information for the diagnosis and treatment of human diseases. The availability and application of genetic information to the understanding of normal and abnormal human growth and development are fundamentally changing the way we approach the study of human diseases. As a result, the issues and principles of medical genetics are coming to bear across all disciplines of health care. In this review, we discuss some of the potential applications of human molecular genetics for the diagnosis and treatment of oral diseases. This discussion is presented in the context of the ongoing technological advances and conceptual changes that are occurring in the field of medical genetics. To realize the promise of this new molecular genetics, we must be prepared to foresee the possibilities and to incorporate these newly emergent technologies into the evolving discipline of dentistry. By using examples of human conditions, we illustrate the broad application of this emerging technology to the study of simple as well as complex genetic diseases. Throughout this paper, we will use the following terminology: Penetrance In a population, defined as the proportion of individuals posessing a disease-causing genotype who express the disease phenotype. When this proportion is less than 100%, the disease is said to have reduced or incomplete penetrance. Polymerase chain reaction (PCR)-A technique for amplifying a large number of copies of a specific DNA sequence flanked by two oligonucleotide primers. The DNA is alternately heated and cooled in the presence of DNA polymerase and free nucleotides, so that the specified DNA segment is denatured, hybridized with primers, and extended by DNA polymerase. MIM-Mendelian Inheritance in Man catalogue number from V. McKusick's Mendelian Inheritance in man (OMIM, 1998).

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Hypophosphatasia with premature shedding of teeth and aplasia of cementum

Cited by 78 publications

References 15 publications

Hypophosphatasia-associated Deficiencies in Mineralization and Gene Expression in Cultured Dental Pulp Cells Obtained from Human Teeth

Hypophosphatasia-associated Deficiencies in Mineralization and Gene Expression in Cultured Dental Pulp Cells Obtained from Human Teeth

Correction of Hypophosphatasia‐Associated Mineralization Deficiencies In Vitro by Phosphate/Pyrophosphate Modulation in Periodontal Ligament Cells

The Impact of Molecular Genetics on Oral Health Paradigms

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