Effects of Active Vitamin D or FGF23 Antibody on Hyp Mice Dentoalveolar Tissues

2021 ◽  
pp. 002203452110110
Author(s):  
E.J. Lira dos Santos ◽  
M.B. Chavez ◽  
M.H. Tan ◽  
F.F. Mohamed ◽  
T.N. Kolli ◽  
...  
Keyword(s):  
Alveolar Bone ◽  
Volume Fraction ◽  
Fibroblast Growth Factor 23 ◽  
Neutralizing Antibody ◽  
Micro Computed Tomography ◽  
Mineral Density ◽  
Bone Volume Fraction ◽  
Treatment Regimens ◽  
New Therapeutic Approaches ◽  
Phex Gene

Mutations in the PHEX gene lead to X-linked hypophosphatemia (XLH), a form of inherited rickets featuring elevated fibroblast growth factor 23 (FGF23), reduced 1,25-dihydroxyvitamin D (1,25D), and hypophosphatemia. Hyp mutant mice replicate the XLH phenotype, including dentin, alveolar bone, and cementum defects. We aimed to compare effects of 1,25D versus FGF23-neutralizing antibody (FGF23Ab) monotherapies on Hyp mouse dentoalveolar mineralization. Male Hyp mice, either injected subcutaneously with daily 1,25D or thrice weekly with FGF23 blocking antibody from 2 to 35 d postnatal, were compared to wild-type (WT) controls and untreated Hyp mice. Mandibles were analyzed by high-resolution micro–computed tomography (micro-CT), histology, and immunohistochemistry. Both interventions maintained normocalcemia, increased serum phosphate levels, and improved dentoalveolar mineralization in treated versus untreated Hyp mice. 1,25D increased crown dentin volume and thickness and root dentin/cementum volume, whereas FGF23Ab effects were limited to crown dentin volume. 1,25D increased bone volume fraction, bone mineral density, and tissue mineral density in Hyp mice, whereas FGF23Ab failed to significantly affect these alveolar bone parameters. Neither treatment fully attenuated dentin and bone defects to WT levels, and pulp volumes remained elevated regardless of treatment. Both treatments reduced predentin thickness and improved periodontal ligament organization, while 1,25D promoted a more profound improvement in acellular cementum thickness. Altered cell densities and lacunocanalicular properties of alveolar and mandibular bone osteocytes and cementocytes in Hyp mice were partially corrected by either treatment. Neither treatment normalized the altered distributions of bone sialoprotein and osteopontin in Hyp mouse alveolar bone. Moderate improvements from both 1,25D and FGF23Ab treatment regimens support further studies and collection of oral health data from subjects receiving a newly approved anti-FGF23 therapy. The inability of either treatment to fully correct Hyp mouse dentin and bone prompts further experiments into underlying pathological mechanisms to identify new therapeutic approaches.

scholarly journals Structure-Function Relationships of the Vertebral Endplate

2021 ◽  
Author(s):  
Yuanqiao Wu ◽  
Elise Feng-i Morgan ◽  
Johnfredy Loaiza ◽  
Rohin Banerji ◽  
Olivia Rose Blouin
Keyword(s):  
Mechanical Properties ◽  
Mechanical Behavior ◽  
Yield Stress ◽  
Volume Fraction ◽  
Level Density ◽  
Micro Computed Tomography ◽  
Vertebral Endplate ◽  
Mineral Density ◽  
Bone Volume Fraction ◽  
Apparent Stiffness

Background: Although deformation and fracture of the vertebral endplate have been implicated in spinal conditions such as vertebral fracture and disc degeneration, few biomechanical studies of this structure are available. The goal of this study was to quantify the mechanical behavior of the vertebral endplate. Methods: Eight-five rectangular specimens were dissected from the superior and/or inferior central endplates of human lumbar spine segments L1-L4. Micro-computed tomography (μCT) imaging, four-point-bend testing, and ashing were performed to quantify the apparent elastic modulus and yield stress (modulus and yield stress, respectively, of the porous vertebral endplate), tissue yield stress (yield stress of the tissue of the vertebral endplate, excluding pores), ultimate strain, fracture strain, bone volume fraction (BV/TV), bone mineral density (BMD), and various measures of tissue density and composition (tissue mineral density, ash fraction, and ash density). Regression was used to assess the dependence of mechanical properties on density and composition. Results: Wide variations in elastic and failure properties, and in density and tissue composition, were observed. BMD and BV/TV were good predictors of many of the apparent-level mechanical properties, including modulus, yield stress, and in the case of the inferior vertebral endplate, failure strains. Similar values of the mechanical properties were noted between superior and inferior vertebral endplates. In contrast to the dependence of apparent stiffness and strength on BMD and BV/TV, none of the mechanical properties depended on any of the tissue-level density measurements. Conclusion: The dependence of many of the mechanical properties of the vertebral endplate on BV/TV and BMD suggests possibilities for non-invasive assessment of how this region of the spine behaves during habitual and injurious loading. Further study of the non-mineral components of the endplate tissue is required to understand how the composition of this tissue may influence the overall mechanical behavior of the vertebral endplate.

scholarly journals Dentoalveolar Defects in the Hyp Mouse Model of X-linked Hypophosphatemia

2020 ◽  
Vol 99 (4) ◽  
pp. 419-428 ◽  
Author(s):  
H. Zhang ◽  
M.B. Chavez ◽  
T.N. Kolli ◽  
M.H. Tan ◽  
H. Fong ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Alveolar Bone ◽  
Volume Fraction ◽  
Fibroblast Growth Factor 23 ◽  
Hypophosphatemic Rickets ◽  
Long Bone ◽  
Micro Ct ◽  
Mineral Density ◽  
Dentin Matrix Protein ◽  
Osteocyte Lacunae

Mutations in PHEX cause X-linked hypophosphatemia (XLH), a form of hypophosphatemic rickets. Hyp ( Phex mutant) mice recapitulate the XLH phenotype. Dental disorders are prevalent in individuals with XLH; however, underlying dentoalveolar defects remain incompletely understood. We analyzed Hyp mouse dentoalveolar defects at 42 and 90 d postnatal to comparatively define effects of XLH on dental formation and function. Phex mRNA was expressed by odontoblasts (dentin), osteocytes (bone), and cementocytes (cellular cementum) in wild-type (WT) mice. Enamel density was unaffected, though enamel volume was significantly reduced in Hyp mice. Dentin defects in Hyp molars were indicated histologically by wide predentin, thin dentin, and extensive interglobular dentin, confirming micro–computed tomography (micro-CT) findings of reduced dentin volume and density. Acellular cementum was thin and showed periodontal ligament detachment. Mechanical testing indicated dramatically altered periodontal mechanical properties in Hyp versus WT mice. Hyp mandibles demonstrated expanded alveolar bone with accumulation of osteoid, and micro-CT confirmed decreased bone volume fraction and alveolar bone density. Cellular cementum area was significantly increased in Hyp versus WT molars owing to accumulation of hypomineralized cementoid. Histology, scanning electron microscopy, and nanoindentation revealed hypomineralized “halos” surrounding Hyp cementocyte and osteocyte lacunae. Three-dimensional micro-CT analyses confirmed larger cementocyte/osteocyte lacunae and significantly reduced perilacunar mineral density. While long bone and alveolar bone osteocytes in Hyp mice overexpressed fibroblast growth factor 23 ( Fgf23), its expression in molars was much lower, with cementocyte Fgf23 expression particularly low. Expression and distribution of other selected markers were disturbed in Hyp versus WT long bone, alveolar bone, and cementum, including osteocyte/cementocyte marker dentin matrix protein 1 ( Dmp1). This study reports for the first time a quantitative analysis of the Hyp mouse dentoalveolar phenotype, including all mineralized tissues. Novel insights into cellular cementum provide evidence for a role for cementocytes in perilacunar mineralization and cementum biology.

scholarly journals Pregnane X receptor knockout mice display osteopenia with reduced bone formation and enhanced bone resorption

2010 ◽  
Vol 207 (3) ◽  
pp. 257-263 ◽  
Author(s):  
Kotaro Azuma ◽  
Stephanie C Casey ◽  
Masako Ito ◽  
Tomohiko Urano ◽  
Kuniko Horie ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Volume Fraction ◽  
Pregnane X Receptor ◽  
Bending Test ◽  
Bone Homeostasis ◽  
Micro Computed Tomography ◽  
Mineral Density ◽  
Bone Volume Fraction ◽  
Trabecular Bones

The steroid and xenobiotic receptor (SXR) and its murine ortholog pregnane X receptor (PXR) are nuclear receptors that are expressed mainly in the liver and intestine where they function as xenobiotic sensors. In addition to its role as a xenobiotic sensor, previous studies in our laboratories and elsewhere have identified a role for SXR/PXR as a mediator of bone homeostasis. Here, we report that systemic deletion of PXR results in marked osteopenia with mechanical fragility in female mice as young as 4 months old. Bone mineral density (BMD) of PXR knockout (PXRKO) mice was significantly decreased compared with the BMD of wild-type (WT) mice. Micro-computed tomography analysis of femoral trabecular bones revealed that the three-dimensional bone volume fraction of PXRKO mice was markedly reduced compared with that of WT mice. Histomorphometrical analysis of the trabecular bones in the proximal tibia showed a remarkable reduction in bone mass in PXRKO mice. As for bone turnover of the trabecular bones, bone formation is reduced, whereas bone resorption is enhanced in PXRKO mice. Histomorphometrical analysis of femoral cortical bones revealed a larger cortical area in WT mice than that in PXRKO mice. WT mice had a thicker cortical width than PXRKO mice. Three-point bending test revealed that these morphological phenotypes actually caused mechanical fragility. Lastly, serum levels of phosphate, calcium, and alkaline phosphatase were unchanged in PXRKO mice compared with WT. Consistent with our previous results, we conclude that SXR/PXR promotes bone formation and suppresses bone resorption thus cementing a role for SXR/PXR as a key regulator of bone homeostasis.

scholarly journals Trabecular bone patterning in the hominoid distal femur

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5156 ◽  
Author(s):  
Leoni Georgiou ◽  
Tracy L. Kivell ◽  
Dieter H. Pahr ◽  
Matthew M. Skinner
Keyword(s):  
Trabecular Bone ◽  
Distal Femur ◽  
Volume Fraction ◽  
Reaction Force ◽  
Intraspecific Variability ◽  
Trabecular Structure ◽  
Trabecular Architecture ◽  
Micro Computed Tomography ◽  
Bone Volume Fraction ◽  
Distal Epiphysis

BackgroundIn addition to external bone shape and cortical bone thickness and distribution, the distribution and orientation of internal trabecular bone across individuals and species has yielded important functional information on how bone adapts in response to load. In particular, trabecular bone analysis has played a key role in studies of human and nonhuman primate locomotion and has shown that species with different locomotor repertoires display distinct trabecular architecture in various regions of the skeleton. In this study, we analyse trabecular structure throughout the distal femur of extant hominoids and test for differences due to locomotor loading regime.MethodsMicro-computed tomography scans ofHomo sapiens(n= 11),Pan troglodytes(n= 18),Gorilla gorilla(n= 14) andPongosp. (n= 7) were used to investigate trabecular structure throughout the distal epiphysis of the femur. We predicted that bone volume fraction (BV/TV) in the medial and lateral condyles inHomowould be distally concentrated and more anisotropic due to a habitual extended knee posture at the point of peak ground reaction force during bipedal locomotion, whereas great apes would show more posteriorly concentrated BV/TV and greater isotropy due to a flexed knee posture and more variable hindlimb use during locomotion.ResultsResults indicate some significant differences between taxa, with the most prominent being higher BV/TV in the posterosuperior region of the condyles inPanand higher BV/TV and anisotropy in the posteroinferior region inHomo. Furthermore, trabecular number, spacing and thickness differ significantly, mainly separatingGorillafrom the other apes.DiscussionThe trabecular architecture of the distal femur holds a functional signal linked to habitual behaviour; however, there was more similarity across taxa and greater intraspecific variability than expected. Specifically, there was a large degree of overlap in trabecular structure across the sample, andHomowas not as distinct as predicted. Nonetheless, this study offers a comparative sample of trabecular structure in the hominoid distal femur and can contribute to future studies of locomotion in extinct taxa.

scholarly journals Effects of different force magnitudes on corticotomy-assisted orthodontic tooth movement in rats

2018 ◽  
Vol 88 (5) ◽  
pp. 632-637 ◽  
Author(s):  
Kriangkrai Kraiwattanapong ◽  
Bancha Samruajbenjakun
Keyword(s):  
Alveolar Bone ◽  
Tooth Movement ◽  
Root Resorption ◽  
Volume Fraction ◽  
Micro Ct ◽  
Histomorphometric Analysis ◽  
Bone Volume Fraction ◽  
Bone Response ◽  
Significant Difference ◽  
Light Force

ABSTRACT Objectives: To investigate the effects of light and heavy forces with corticotomy on tooth movement rate, alveolar bone response, and root resorption in a rat model. Materials and Methods: The right and left sides of 40 male Wistar rats were randomly assigned using the split-mouth design to two groups: light force with corticotomy (LF) and heavy force with corticotomy (HF). Tooth movement was performed on the maxillary first molars using a nickel-titanium closed-coil spring delivering either 10 g (light force) or 50 g (heavy force). Tooth movement and alveolar bone response were assessed by micro–computed tomography (micro-CT) at day 0 as the baseline and on days 7, 14, 21, and 28. Root resorption was examined by histomorphometric analysis at day 28. Results: Micro-CT analysis showed a significantly greater tooth movement in the HF group at days 7 and 14 but no difference in bone volume fraction at any of the observed periods. Histomorphometric analysis found no significant difference in root resorption between the LF and HF groups at day 28. Conclusions: Heavy force with corticotomy increased tooth movement at days 7 and 14 but did not show any difference in alveolar bone change or root resorption.

scholarly journals Targeted ablation of the PTH/PTHrP receptor in osteocytes impairs bone structure and homeostatic calcemic responses

2011 ◽  
Vol 209 (1) ◽  
pp. 21-32 ◽  
Author(s):  
William F Powell ◽  
Kevin J Barry ◽  
Irena Tulum ◽  
Tatsuya Kobayashi ◽  
Stephen E Harris ◽  
...  
Keyword(s):  
Volume Fraction ◽  
Bone Structure ◽  
Micro Computed Tomography ◽  
Bone Volume Fraction ◽  
Blood Calcium ◽  
Low Calcium Diet ◽  
Exon 1 ◽  
Skeletal Homeostasis ◽  
Pthrp Receptor

Parathyroid hormone (PTH) is a major physiologic regulator of calcium, phosphorous, and skeletal homeostasis. Cells of the osteoblastic lineage are key targets of PTH action in bone, and recent evidence suggests that osteocytes might be important in the anabolic effects of PTH. To understand the role of PTH signaling through the PTH/PTHrP receptors (PPR) in osteocytes and to determine the role(s) of these cells in mediating the effects of the hormone, we have generated mice in which PPR expression is specifically ablated in osteocytes. Transgenic mice in which the 10 kb-Dmp1 promoter drives a tamoxifen-inducible Cre-recombinase were mated with animals in which exon 1 of PPR is flanked by lox-P sites. In these animals, osteocyte-selective PPR knockout (Ocy-PPRcKO mice) could be induced by administration of tamoxifen. Histological analysis revealed a reduction in trabecular bone and mild osteopenia in Ocy-PPRcKO mice. Reduction of trabeculae number and thickness was also detected by micro-computed tomography analysis whereas bone volume fraction (BV/TV%) was unchanged. These findings were associated with an increase in Sost and sclerostin expression. When Ocy-PPRcKO mice were subjected to a low-calcium diet to induce secondary hyperparathyroidism, their blood calcium levels were significantly lower than littermate controls. Moreover, PTH was unable to suppress Sost and sclerostin expression in the Ocy-PPRcKO animals, suggesting an important role of PTH signaling in osteocytes for proper bone remodeling and calcium homeostasis.

scholarly journals Distribution of mandibular trabeculae bone volume fraction in relation to different MOP intervals for accelerating orthodontic tooth movement:

2020 ◽  
Vol 90 (6) ◽  
pp. 774-782
Author(s):  
Ng Heng Khiang Teh ◽  
Saritha Sivarajan ◽  
Muhammad Khan Asif ◽  
Norliza Ibrahim ◽  
Mang Chek Wey
Keyword(s):  
Alveolar Bone ◽  
Tooth Movement ◽  
Volume Fraction ◽  
Orthodontic Tooth Movement ◽  
Bone Volume ◽  
Mean Difference ◽  
Bone Volume Fraction ◽  
Interval Group ◽  
Canine Retraction ◽  
Computed Tomography Images

ABSTRACT Objectives To investigate the effect of micro-osteoperforation (MOP) on the horizontal and vertical distribution of mandibular trabeculae bone volume fraction in relation to different MOP intervals during canine retraction. Materials and Methods This single-center, single-blinded, prospective randomized split-mouth clinical trial included 30 healthy participants aged 18 years and older, randomized into three groups of different MOP intervals (4, 8, and 12-weekly). Cone beam computed tomography images were taken to assess the bone volume fraction (bone volume over total volume or BV/TV). Results BV/TV was significantly reduced (mean difference: 9.79%, standard deviation [SD]: 11.89%; 95% confidence interval [CI]: 4.77, 14.81%; P < .01) and canine retraction increased (mean difference: -1.25 mm/4 mo, SD: 0.79 mm; 95% CI: -1.59, -0.92 mm; P < .01) with MOP, compared to control sites. MOP significantly changed the vertical and horizontal patterns of trabeculae bone with lower values nearer to intervention sites. Only the 4-weekly MOP interval group showed significant decrease in BV/TV (mean difference: 14.73%, SD: 12.88%; 95% CI: 3.96, 25.50%; P = .01) despite significant increase in canine retraction rate for all interval groups. With the use of MOP, BV/TV was found to be inversely correlated to the rate of canine retraction (r = -0.425; P = .04). Conclusions Mandibular trabecular alveolar bone volume fraction was reduced and rate of orthodontic tooth movement increased with MOP, especially in the 4-weekly interval. However, this effect was limited to the immediate interdental region of MOP.

scholarly journals Increased Microstructural Variability Is Associated With Decreased Structural Strength but With Increased Measures of Structural Ductility in Human Vertebrae

2009 ◽  
Author(s):  
Janardhan Yerramshetty ◽  
Do-Gyoon Kim ◽  
Yener N. Yeni
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Volume Fraction ◽  
Structural Parameters ◽  
Average Density ◽  
Mineral Density ◽  
Bone Volume Fraction ◽  
Microstructural Parameters ◽  
Apparent Modulus ◽  
Vertebral Strength

The lack of accuracy in the prediction of vertebral fracture risk from average density measurements, all external factors being equal, may be because bone mineral density (BMD) is less than a perfect surrogate for bone strength but also because strength alone may not be sufficient to fully characterize the structural failure of a vertebra. Apart from bone quantity, organization of micro-architecture would have a role in governing mechanical properties of vertebrae. An earlier study indicated that within-vertebra variability, measured as the coefficient of variation (COV) of bone volume fraction (BV/TV) or as COV of finite element-estimated apparent modulus (EFE) correlated well with vertebral strength [1]. Therefore, as an extension to our earlier study, we investigated i) whether the relationships of vertebral strength found with COV of BV/TV and COV of EFE could be extended to the COV of other micro-structural parameters and microcomputed tomography-estimated bone mineral density (μCT-BMD) and ii) whether COV of microstructural parameters were associated with structural ductility measures.

scholarly journals In vivo microcomputed tomography evaluation of rat alveolar bone and root resorption during orthodontic tooth movement

2012 ◽  
Vol 83 (3) ◽  
pp. 402-409 ◽  
Author(s):  
Nan Ru ◽  
Sean Shih-Yao Liu ◽  
Li Zhuang ◽  
Song Li ◽  
Yuxing Bai
Keyword(s):  
Alveolar Bone ◽  
Tooth Movement ◽  
Root Resorption ◽  
Volume Fraction ◽  
Orthodontic Tooth Movement ◽  
Bone Volume ◽  
Structure Model ◽  
Bone Volume Fraction ◽  
Trabecular Thickness

ABSTRACT Objective: To observe the real-time microarchitecture changes of the alveolar bone and root resorption during orthodontic treatment. Materials and Methods: A 10 g force was delivered to move the maxillary left first molars mesially in twenty 10-week-old rats for 14 days. The first molar and adjacent alveolar bone were scanned using in vivo microcomputed tomography at the following time points: days 0, 3, 7, and 14. Microarchitecture parameters, including bone volume fraction, structure model index, trabecular thickness, trabecular number, and trabecular separation of alveolar bone, were measured on the compression and tension side. The total root volume was measured, and the resorption crater volume at each time point was calculated. Univariate repeated measures analysis of variance with Bonferroni corrections were performed to compare the differences in each parameter between time points with significance level at P < .05. Results: From day 3 to day 7, bone volume fraction, structure model index, trabecular thickness, and trabecular separation decreased significantly on the compression side, but the same parameters increased significantly on the tension side from day 7 to day 14. Root resorption volume of the mesial root increased significantly on day 7 of orthodontic loading. Conclusions: Real-time root and bone resorption during orthodontic movement can be observed in 3 dimensions using in vivo micro-CT. Alveolar bone resorption and root resorption were observed mostly in the apical third on day 7 on the compression side; bone formation was observed on day 14 on the tension side during orthodontic tooth movement.

scholarly journals Antiosteoporosis Effect ofRadix ScutellariaeExtract on Density and Microstructure of Long Bones in Tail-Suspended Sprague-Dawley Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Chen-Rui Li ◽  
Guang-Wei Zhang ◽  
Yin-Bo Niu ◽  
Ya-Lei Pan ◽  
Yuan-Kun Zhai ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Volume Fraction ◽  
Bone Microarchitecture ◽  
Osteoclast Differentiation ◽  
Hindlimb Unloading ◽  
Mineral Density ◽  
Bone Volume Fraction ◽  
Trabecular Thickness ◽  
Radix Scutellariae

Radix Scutellariae (RS), a medicinal herb, is extensively employed in traditional Chinese medicines and modern herbal prescriptions. Two major flavonoids in RS were known to induce osteoblastic differentiation and inhibit osteoclast differentiation, respectively. This study aimed to investigate the effect ofRadix Scutellariaeextract (RSE) against bone loss induced by mechanical inactivity or weightlessness. A hindlimb unloading tail-suspended rat model (TS) was established to determine the effect of RSE on bone mineral density and bone microarchitecture. Treatment of RSE at 50 mg/kg/day and alendronate (ALE) at 2 mg/kg/day as positive control for 42 days significantly increased the bone mineral density and mechanical strength compared with TS group. Enhanced bone turnover markers by TS treatment were attenuated by RSE and ALE administration. Deterioration of bone trabecula induced by TS was prevented. Moreover, both treatments counteracted the reduction of bone volume fraction, trabecular thickness and number, and connectivity density. In conclusion, RSE was demonstrated for the first time to prevent osteoporosis induced by TS treatment, which suggests the potential application of RSE in the treatment of disuse-induced osteoporosis.

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