Loss of Discoidin Domain Receptor 1 Predisposes Mice to Periodontal Breakdown

Chavez, Michael B.; Kolli, Tamara N.; Tan, Mingyue; Zachariadou, Christina; Wang, C.; Embree, Mildred C.; Santos, Elis Janaína Lira dos; Nociti, Francisco Humberto; Wang, Y.; Tatakis, Dimitris N.; Agarwal, Gunjan; Foster, Brian L.

doi:10.1177/0022034519881136

Cited by 13 publications

(35 citation statements)

References 34 publications

(42 reference statements)

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“…These also have their own capabilities and limitations that dictate to some degree the ease and efficiency of analysis. All analyses and images included in this report were accomplished using Scanco proprietary software for scan reconstructions (default settings) and AnalyzePro 1.0 medical imaging software (Analyze Direct, Overland Park, KS), a software system used in our studies (23,(44)(45)(46)(47)(48)(49).…”

Section: Image Acquisition Of Dentoalveolar Tissuesmentioning

confidence: 99%

“…4A1-3). In mouse studies where molars are erupted and amelogenesis has been completed, we typically threshold enamel at >1,600 mg HA/cm³ (44,45,48,49). After thresholding and confirming segmentation of enamel from dentin, enamel volume and average mineral density are easily calculated.…”

Section: Enamelmentioning

confidence: 99%

“…In a study to define the dentoalveolar functions of discoidin domain receptor 1 (DDR1), a collagen receptor tyrosine kinase that regulates cell functions and collagen fibrillogenesis and mineralization, mice genetically ablated for Ddr1 (Ddr1 -/-) exhibited severe alveolar bone loss with age ( Fig. 5D) (44). In that study, we employed microCT in three ways to quantify alveolar bone loss in this model: linear measurements, total alveolar bone volume, and a novel approach to measure "alveolar bone proper" (ABP) immediately adjacent to molar roots.…”

Section: Alveolar Bonementioning

confidence: 99%

“…WT molars. Locations are indicated by tooth (1-3) and direction or feature (M, mesial; D; distal; B; buccal; L, lingual; C, cusp; G, groove), as described in (44). Second, measurement of total alveolar bone loss around molars reveals 14% reduction in Ddr1 -/vs.…”

Section: Summary Of Guidelinesmentioning

confidence: 99%

“…All analyses and images included in this report were accomplished using Scanco proprietary software for scan reconstructions (default settings) and AnalyzePro 1.0 medical imaging software (Analyze Direct, Overland Park, KS), a software system used in our studies. (23,(44)(45)(46)(47)(48)(49) CT images are created using X-rays directed and rotated around a sample (or a sample rotating in relation to the X-ray source), creating a series of projections. X-rays are a form of electromagnetic radiation with high photon energy, and image generation relies on the partial transmission of X-rays; ie, differential absorption of X-rays by tissues.…”

Section: Image Acquisition Of Dentoalveolar Tissuesmentioning

confidence: 99%

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Guidelines for Micro–Computed Tomography Analysis of Rodent Dentoalveolar Tissues

et al. 2021

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Section: Image Acquisition Of Dentoalveolar Tissuesmentioning

confidence: 99%

Section: Enamelmentioning

confidence: 99%

Section: Alveolar Bonementioning

confidence: 99%

Section: Summary Of Guidelinesmentioning

confidence: 99%

Section: Image Acquisition Of Dentoalveolar Tissuesmentioning

confidence: 99%

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Guidelines for Micro–Computed Tomography Analysis of Rodent Dentoalveolar Tissues

et al. 2021

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Dentoalveolar Defects of Hypophosphatasia are Recapitulated in a Sheep Knock-In Model

Mohamed

Chavez

Huggins

et al. 2020

Journal of Bone and Mineral Research

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Hypophosphatasia (HPP) is the inherited error-of-metabolism caused by mutations in ALPL, reducing the function of tissuenonspecific alkaline phosphatase (TNAP/TNALP/TNSALP). HPP is characterized by defective skeletal and dental mineralization and is categorized into several clinical subtypes based on age of onset and severity of manifestations, though premature tooth loss from acellular cementum defects is common across most HPP subtypes. Genotype-phenotype associations and mechanisms underlying musculoskeletal, dental, and other defects remain poorly characterized. Murine models that have provided significant insights into HPP pathophysiology also carry limitations including monophyodont dentition, lack of osteonal remodeling of cortical bone, and differing patterns of skeletal growth. To address this, we generated the first gene-edited large-animal model of HPP in sheep via CRISPR/Cas9-mediated knock-in of a missense mutation (c.1077C>G; p.I359M) associated with skeletal and dental manifestations in humans. We hypothesized that this HPP sheep model would recapitulate the human dentoalveolar manifestations of HPP. Compared to wild-type (WT), compound heterozygous (cHet) sheep with one null allele and the other with the targeted mutant allele exhibited the most severe alveolar bone, acellular cementum, and dentin hypomineralization defects. Sheep homozygous for the mutant allele (Hom) showed alveolar bone and hypomineralization effects and trends in dentin and cementum, whereas sheep heterozygous (Het) for the mutation did not exhibit significant effects. Important insights gained include existence of early alveolar bone defects that may contribute to tooth loss in HPP, observation of severe mantle dentin hypomineralization in an HPP animal model, association of cementum hypoplasia with genotype, and correlation of dentoalveolar defects with alkaline phosphatase (ALP) levels. The sheep model of HPP faithfully recapitulated dentoalveolar defects reported in individuals with HPP, providing a new translational model for studies into etiopathology and novel therapies of this disorder, as well as proof-of-principle that genetically engineered large sheep models can replicate human dentoalveolar disorders.

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Dentoalveolar Alterations in an Adenine‐Induced Chronic Kidney Disease Mouse Model

Mohamed,

Amadeu de Oliveira,

Kinoshita

et al. 2023

J of Bone & Mineral Res

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Chronic kidney disease (CKD) is characterized by kidney damage and loss of renal function. CKD mineral and bone disorder (CKD–MBD) describes the dysregulation of mineral homeostasis, including hyperphosphatemia and elevated parathyroid hormone (PTH) secretion, skeletal abnormalities, and vascular calcification. CKD–MBD impacts the oral cavity, with effects including salivary gland dysfunction, enamel hypoplasia and damage, increased dentin formation, decreased pulp volume, pulp calcifications, and altered jaw bones, contributing to clinical manifestations of periodontal disease and tooth loss. Underlying mechanisms are not fully understood, and CKD mouse models commonly require invasive procedures with high rates of infection and mortality. We aimed to characterize the dentoalveolar effects of an adenine diet (AD)‐induced CKD (AD–CKD) mouse model. Eight‐week‐old C57BL/6J mice were provided either a normal phosphorus diet control (CTR) or adenine and high‐phosphorus diet CKD to induce kidney failure. Mice were euthanized at 15 weeks old, and mandibles were collected for micro–computed tomography and histology. CKD mice exhibited kidney failure, hyperphosphatemia, and hyperparathyroidism in association with porous cortical bone in femurs. CKD mice showed a 30% decrease in molar enamel volume compared to CTR mice. Enamel wear was associated with reduced ductal components, ectopic calcifications, and altered osteopontin (OPN) deposition in submandibular salivary glands of CKD mice. Molar cusps in CKD mice were flattened, exposing dentin. Molar dentin/cementum volume increased 7% in CKD mice and pulp volume decreased. Histology revealed excessive reactionary dentin and altered pulp‐dentin extracellular matrix proteins, including increased OPN. Mandibular bone volume fraction decreased 12% and bone mineral density decreased 9% in CKD versus CTR mice. Alveolar bone in CKD mice exhibited increased tissue‐nonspecific alkaline phosphatase localization, OPN deposition, and greater osteoclast numbers. AD–CKD recapitulated key aspects reported in CKD patients and revealed new insights into CKD‐associated oral defects. This model has potential for studying mechanisms of dentoalveolar defects or therapeutic interventions. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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Loss of Discoidin Domain Receptor 1 Predisposes Mice to Periodontal Breakdown

Cited by 13 publications

References 34 publications

Guidelines for Micro–Computed Tomography Analysis of Rodent Dentoalveolar Tissues

Guidelines for Micro–Computed Tomography Analysis of Rodent Dentoalveolar Tissues

Dentoalveolar Defects of Hypophosphatasia are Recapitulated in a Sheep Knock-In Model

Dentoalveolar Alterations in an Adenine‐Induced Chronic Kidney Disease Mouse Model

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