Altering calcium and phosphorus levels in utero affects adult mouse mandibular morphology

Hassan, Mohamed; Vargas, Rubem Mário Figueiró; Zaher, Abbas; Ismail, Hassan; Lee, Clare; Cox, Timothy C.; Jheon, Andrew H.

doi:10.1111/ocr.12269

Cited by 8 publications

(15 citation statements)

References 32 publications

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“…Sex dimorphism affecting mandibles, cartilage, and Klotho protein expression after feeding low Pi diet has also been reported in other mouse models but whether sex hormones are responsible for the sex-specific phenotype is unknown. (30,34,35) Sex steroids, mainly estrogen and testosterone, have been associated with bone health via inhibitory effects on bone resorption or stimulatory effects on bone formation in a compartment-specific manner (cortical versus cancellous bone). (36,37) Whether Pi intake influences sex hormone levels and whether Pi interacts with Effects of reduced PPi concentration on BMSC and BMM cultures derived from Ank +/+ and Ank KI/KI mice.…”

Section: Discussionmentioning

confidence: 99%

Restriction of Dietary Phosphate Ameliorates Skeletal Abnormalities in a Mouse Model for Craniometaphyseal Dysplasia

Fujii

Kozák

Dutra

et al. 2020

Journal of Bone and Mineral Research

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Craniometaphyseal dysplasia (CMD), a rare genetic bone disorder, is characterized by lifelong progressive thickening of craniofacial bones and metaphyseal flaring of long bones. The autosomal dominant form of CMD is caused by mutations in the progressive ankylosis gene ANKH (mouse ortholog Ank), encoding a pyrophosphate (PPi) transporter. We previously reported reduced formation and function of osteoblasts and osteoclasts in a knockin (KI) mouse model for CMD (Ank KI/KI) and in CMD patients. We also showed rapid protein degradation of mutant ANK/ANKH. Mutant ANK protein displays reduced PPi transport, which may alter the inorganic phosphate (Pi) and PPi ratio, an important regulatory mechanism for bone mineralization. Here we investigate whether reducing dietary Pi intake can ameliorate the CMD-like skeletal phenotype by comparing male and female Ank +/+ and Ank KI/KI mice exposed to a low (0.3%) and normal (0.7%) Pi diet for 13 weeks from birth. Serum Pi and calcium (Ca) levels were not significantly changed by diet, whereas PTH and 25-hydroxy vitamin D (25-OHD) were decreased by low Pi diet but only in male Ank +/+ mice. Importantly, the 0.3% Pi diet significantly ameliorated mandibular hyperostosis in both sexes of Ank KI/KI mice. A tendency of decreased femoral trabeculation was observed in male and female Ank +/+ mice as well as in male Ank KI/KI mice fed with the 0.3% Pi diet. In contrast, in female Ank KI/KI mice the 0.3% Pi diet resulted in increased metaphyseal trabeculation. This was also the only group that showed increased bone formation rate. Low Pi diet led to increased osteoclast numbers and increased bone resorption in all mice. We conclude that lowering but not depleting dietary Pi delays the development of craniofacial hyperostosis in CMD mice without severely compromising serum levels of Pi, Ca, PTH, and 25-OHD. These findings may have implications for better clinical care of patients with CMD.

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Section: Discussionmentioning

confidence: 99%

Restriction of Dietary Phosphate Ameliorates Skeletal Abnormalities in a Mouse Model for Craniometaphyseal Dysplasia

Fujii

Kozák

Dutra

et al. 2020

Journal of Bone and Mineral Research

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“…Our studies are the first to exploit GMA to catalog three‐dimensional (3D) morphologic changes in the mandibular condyles. ( 30,31 ) Furthermore, both experimental condylar processes showed an ~15% decrease in total bone volume but an ~5% increase in BMD compared to control condyles. Increased degenerative changes were noted in both left and right condyles from experimental mice, and the proliferative and differentiated cartilage zones within the MCC were altered with a shift toward markers of maturation and hypertrophic chondrocytes.…”

Section: Discussionmentioning

confidence: 92%

“…2 A , A' ) and performed GMA. ( 30,31 ) Semi‐landmarking analysis revealed an increase in convexity at the condylar surface and a narrowing of the condylar head and neck in both the anteroposterior and mediolateral dimensions in experimental condyles. Specifically, control and experimental right/extraction side condyles clustered distinctly along PC1 (50.05%) and PC2 (10.09%; Fig.…”

Section: Resultsmentioning

confidence: 98%

Unilateral Loss of Maxillary Molars in Young Mice Leads to Bilateral Condylar Adaptation and Degenerative Disease

Chen

Zhang

et al. 2022

JBMR Plus

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The adaptive response of the mandible and temporomandibular joint (TMJ) to altered occlusion in juvenile patients is presently unclear. To address this question, we established a mouse model in which all molars were extracted from the maxillary right quadrant in prepubertal, 3-week-old mice and analyzed morphological, tissue, cellular, and molecular changes in the mandible and condyle 3 weeks later. Unilateral loss of maxillary molars led to significant, robust, bilateral changes, primarily in condylar morphology, including anteroposterior narrowing of the condylar head and neck and increased convexity at the condylar surface, as determined by geometric morphometric analysis. Furthermore, both condyles in experimental mice exhibited a degenerative phenotype, which included decreased bone volume and increased mineral density near the condylar head surface compared to control mice. Changes in condylar morphology and mineralized tissue composition were associated with alterations in the cellular architecture of the mandibular condylar cartilage, including increased expression of markers for mature (Col2a1) and hypertrophic (Col10a1) chondrocytes, suggesting a shift toward differentiating chondrocytes. Our results show significant bilateral condylar morphological changes, alterations in tissue composition, cellular organization, and molecular expression, as well as degenerative disease, in response to the unilateral loss of teeth. Our study provides a relatively simple, tractable mouse tooth extraction system that will be of utility in uncovering the cellular and molecular mechanisms of condylar and mandibular adaptation in response to altered occlusion.

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“…A study on time-mated FVB wild-type mice and fed high-calcium, low-phosphorus diets in utero up to weaning age showed morphological changes and bone mineral density differences in the jaws of offspring exposed to this experimental diet: retrognathic mandibles associated with a reduced bone mineral density in females, mandibles with height and length of the mandibular body increased in males with condyles similar to those observed in females. Altering calcium and phosphorus levels in utero affects adult mouse mandibular morphology [30,40].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Vitamin D (25OHD), Bone Alkaline Phosphatase (BALP), Serum Calcium, Serum Phosphorus, Ionized Calcium in Patients with Mandibular Third Molar Impaction. An Observational Study

et al. 2021

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The aim of this study was to evaluate the levels of vitamin D (25OHD) and other bone biomarkers in patients with third molar impaction (TMI). Thirty males and 30 females with unilateral or bilateral impacted mandibular third molar, and 15 males and 15 females as a control group (CG) were recruited. Rx-OPT was used to evaluate dental position and Pederson index to measure the difficulty of the intervention. Bone biomarkers were measured through blood venous sample in TMI group and CG. Mann-Whitney test, Pearson’s correlation coefficient, linear regression model were used to compare the different parameters in the two groups. 25OHD showed lower values in TMI group than in CG (p < 0.05) with values significantly lower in bilateral impaction (p < 0.05). Pearson’s coefficient for 25OHD presented a negative correlation with the Pederson index (ρ = −0.75). Bone alkaline phosphatase (BALP) showed significantly lower dosage in TMI group than CG (p = 0.02), Pearson’s coefficient for BALP presented a negative correlation with the Pederson index. Serum calcium, serum phosphorus, ionized calcium levels in TMI and CG groups were similar and Mann-Whitney test did not significantly differ between TMI and CG. TMI could be a sign of vitamin D deficiency and of low BALP levels that should be investigated.

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Altering calcium and phosphorus levels in utero affects adult mouse mandibular morphology

Cited by 8 publications

References 32 publications

Restriction of Dietary Phosphate Ameliorates Skeletal Abnormalities in a Mouse Model for Craniometaphyseal Dysplasia

Restriction of Dietary Phosphate Ameliorates Skeletal Abnormalities in a Mouse Model for Craniometaphyseal Dysplasia

Unilateral Loss of Maxillary Molars in Young Mice Leads to Bilateral Condylar Adaptation and Degenerative Disease

Evaluation of Vitamin D (25OHD), Bone Alkaline Phosphatase (BALP), Serum Calcium, Serum Phosphorus, Ionized Calcium in Patients with Mandibular Third Molar Impaction. An Observational Study

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