scholarly journals Skeletal Toxicity of Coplanar Polychlorinated Biphenyl Congener 126 in the Rat Is Aryl Hydrocarbon Receptor Dependent

2020 ◽  
Vol 175 (1) ◽  
pp. 113-125 ◽  
Author(s):  
Ashlee E Williams ◽  
James Watt ◽  
Larry W Robertson ◽  
Gopi Gadupudi ◽  
Michele L Osborn ◽  
...  
Keyword(s):  
Growth Plate ◽  
Bone Growth ◽  
Polychlorinated Biphenyl ◽  
Corn Oil ◽  
Specific Effect ◽  
Tissue Growth ◽  
Bone Formation Rate ◽  
Bone Length ◽  
Dynamic Histomorphometry ◽  
Pcb 126

Abstract Epidemiological evidence links polychlorinated biphenyls (PCBs) to skeletal toxicity, however mechanisms whereby PCBs affect bone are poorly studied. In this study, coplanar PCB 126 (5 μmol/kg) or corn oil vehicle was administered to N = 5 and 6 male and female, wild type (WT) or AhR −/− rats via intraperitoneal injection. Animals were sacrificed after 4 weeks. Bone length was measured; bone morphology was assessed by microcomputed tomography and dynamic histomorphometry. Reduced bone length was the only genotype-specific effect and only observed in males (p < .05). WT rats exposed to PCB 126 had reduced serum calcium, and smaller bones with reduced tibial length, cortical area, and medullary area relative to vehicle controls (p < .05). Reduced bone formation rate observed in dynamic histomorphometry was consistent with inhibition of endosteal and periosteal bone growth. The effects of PCB 126 were abolished in AhR −/− rats. Gene expression in bone marrow and shaft were assessed by RNA sequencing. Approximately 75% of the PCB-regulated genes appeared AhR dependent with 89 genes significantly (p < .05) regulated by both PCB 126 and knockout of the AhR gene. Novel targets significantly induced by PCB 126 included Indian hedgehog (Ihh) and connective tissue growth factor (Ctgf/Ccn2), which regulate chondrocyte proliferation and differentiation in the bone growth plate and cell-matrix interactions. These data suggest the toxic effects of PCB 126 on bone are mediated by AhR, which has direct effects on the growth plate and indirect actions related to endocrine disruption. These studies clarify important mechanisms underlying skeletal toxicity of dioxin-like PCBs and highlight potential therapeutic targets.

A TECHNIQUE FOR MEASURING LINEAR BONE GROWTH DURING SHORT TIME INTERVALS IN CATTLE

1981 ◽  
Vol 61 (4) ◽  
pp. 1049-1053
Author(s):  
W. C. GRAHAM ◽  
M. A. PRICE
Keyword(s):  
Growth Plate ◽  
Ultraviolet Light ◽  
Present Experiment ◽  
Bone Growth ◽  
Age Groups ◽  
Epiphyseal Growth Plate ◽  
Time Intervals ◽  
Bone Length ◽  
Green Fluorescent ◽  
Short Time

A technique is described for meausuring increases in bone length during defined periods before slaughter in cattle. It consists of jugular infusions of oxytetracycline at specified time intervals. Oxytetracycline identifies the sites of ossification in growing bones at the time of infusion by leaving a label which can be seen as a yellow-green fluorescent line under ultraviolet light. By applying a series of labels at known time intervals, the amount and rate of bone growth at any particular site during those time intervals can be determined. In the present experiment the distal epiphyseal growth plate in the radiuses of young cows (five 2-yr-olds, five 3-yr-olds and four 4-yr-olds) were studied. The increase in bone length at that site for the three age groups was found to be 0.0732, 0.0205 and 0.0000 mm/day respectively.

Polychlorinated biphenyl induced hepatocyte alterations

1987 ◽  
Vol 45 ◽  
pp. 716-717
Author(s):  
D.N. Collins ◽  
J.N. Turner ◽  
K.O. Brosch ◽  
R.F. Seegal
Keyword(s):  
Lipid Droplets ◽  
Wistar Rats ◽  
Homovanillic Acid ◽  
Polychlorinated Biphenyl ◽  
Corn Oil ◽  
Environmental Pollutants ◽  
Short Term ◽  
Pcb Congeners ◽  
Urinary Levels ◽  
The Brain

Polychlorinated biphenyls (PCBs) are a ubiquitous class of environmental pollutants with toxic and hepatocellular effects, including accumulation of fat, proliferated smooth endoplasmic recticulum (SER), and concentric membrane arrays (CMAs) (1-3). The CMAs appear to be a membrane storage and degeneration organelle composed of a large number of concentric membrane layers usually surrounding one or more lipid droplets often with internalized membrane fragments (3). The present study documents liver alteration after a short term single dose exposure to PCBs with high chlorine content, and correlates them with reported animal weights and central nervous system (CNS) measures. In the brain PCB congeners were concentrated in particular regions (4) while catecholamine concentrations were decreased (4-6). Urinary levels of homovanillic acid a dopamine metabolite were evaluated (7).Wistar rats were gavaged with corn oil (6 controls), or with a 1:1 mixture of Aroclor 1254 and 1260 in corn oil at 500 or 1000 mg total PCB/kg (6 at each level).

scholarly journals Micro-CT data of early physiological cancellous bone formation in the lumbar spine of female C57BL/6 mice

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Michael Zenzes ◽  
Paul Zaslansky
Keyword(s):  
Cancellous Bone ◽  
Structural Changes ◽  
Bone Growth ◽  
Post Partum ◽  
Three Dimensional ◽  
Lumbar Vertebra ◽  
Tissue Growth ◽  
Micro Ct ◽  
Mineral Density ◽  
Ct Data

AbstractMicro-CT provides critical data for musculoskeletal research, yielding three-dimensional datasets containing distributions of mineral density. Using high-resolution scans, we quantified changes in the fine architecture of bone in the spine of young mice. This data is made available as a reference to physiological cancellous bone growth. The scans (n = 19) depict the extensive structural changes typical for female C57BL/6 mice pups, aged 1-, 3-, 7-, 10- and 14-days post-partum, as they attain the mature geometry. We reveal the micro-morphology down to individual trabeculae in the spine that follow phases of mineral-tissue rearrangement in the growing lumbar vertebra on a micrometer length scale. Phantom data is provided to facilitate mineral density calibration. Conventional histomorphometry matched with our micro-CT data on selected samples confirms the validity and accuracy of our 3D scans. The data may thus serve as a reference for modeling normal bone growth and can be used to benchmark other experiments assessing the effects of biomaterials, tissue growth, healing, and regeneration.

scholarly journals Bone, Growth Plate and Mineral Metabolism

2010 ◽  
pp. 65-81 ◽  
Author(s):  
Terhi Heino ◽  
Dov Tiosano ◽  
Aneta Gawlik ◽  
Lars Sävendahl
Keyword(s):  
Growth Plate ◽  
Bone Growth ◽  
Mineral Metabolism

scholarly journals Effect of Pulsed Electromagnetic Field Stimulation on the Growth Plate of the Tibia Bone of Rats: An In Vivo Study

2021 ◽  
Vol 11 (16) ◽  
pp. 7571
Author(s):  
Yoon-Young Sung ◽  
Jae-Woo Shin ◽  
Won-Kyung Yang ◽  
Min-Jin Kim ◽  
Ja-Ik Koo ◽  
...  
Keyword(s):  
Electromagnetic Field ◽  
Growth Plate ◽  
Bone Growth ◽  
Articular Chondrocytes ◽  
Growth Promotion ◽  
Control Group ◽  
Pulsed Electromagnetic Field ◽  
Tibia Bone ◽  
Pulsed Electromagnetic

Currently, many children undergo precocious puberty, resulting in short stature due to premature closure of the growth plate. Pulsed electromagnetic field (PEMF) stimulation induces cell proliferation of articular chondrocytes. We developed a method for growth promotion using equipment with PEMF. In this study, we aimed to evaluate the effects of PEMF on the growth rate of growth plates using an animal model. An experimental study was conducted on 16 3-week-old rats to validate the effects of the growth care device on growth and development by PEMF stimulation at 28 Hz and 20 Gauss. The tibia bones of the groups with and without PEMF administration were dissected after 10 days, and then, the length of the growth plate of the knee and levels of insulin-like growth factor (IGF)-1 hormone in serum were measured. The length of the growth plate on the tibia bone and the levels of circulating IGF-1 were significantly increased by 25.6% and 13.6%, respectively, in the experimental group to which PEMF was applied compared to those of the control group, without any side effects. These results suggest that PEMF can safely stimulate growth of the growth plate in a non-invasive manner to promote bone growth.

scholarly journals Long Term Cyclic Pamidronate Reduces Bone Growth by Inhibiting Osteoclast Mediated Cartilage-to-Bone Turnover in the Mouse

2008 ◽  
Vol 2 (1) ◽  
pp. 121-125 ◽  
Author(s):  
K.D Evans ◽  
L.E Sheppard ◽  
D.I Grossman ◽  
S.H Rao ◽  
R.B Martin ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Growth Plate ◽  
Bone Growth ◽  
Cathepsin K ◽  
Chondrocyte Apoptosis ◽  
Cell Numbers ◽  
Hypertrophic Chondrocyte ◽  
Osteoclast Function ◽  
And Function

Bisphosphonates, used to treat diseases exhibiting increased osteoclast activity, reduce longitudinal bone growth through an as yet undefined mechanism. Pamidronate, an aminobisphosphonate, was given weekly to mice at 0, 1.25, or 2.50 mg/kg/wk beginning at 4 weeks of age. At 12 weeks of age, humeral length, growth plate area, regional chondrocyte cell numbers, chondrocyte apoptosis, TRAP stained osteoclast number, and osteoclast function assessed by cathepsin K immunohistochemistry were quantified. Humeral length was decreased in pamidronate treated mice compared to vehicle control mice, and correlated with greater growth plate areas reflecting greater proliferative and hypertrophic chondrocyte cell numbers with fewer hypertrophic cells undergoing apoptosis. Pamidronate treatment increased TRAP stained osteoclast numbers yet decreased cathepsin K indicating that pamidronate repressed osteoclast maturation and function. The data suggest that long term cyclic pamidronate treatment impairs bone growth by inhibition of osteoclast maturation thereby reducing cartilage-to-bone turnover within the growth plate.

scholarly journals Exposure to the RXR agonist SR11237 in early life causes disturbed skeletal morphogenesis in a rat model

2019 ◽  
Author(s):  
Holly Dupuis ◽  
Michael Andrew Pest ◽  
Ermina Hadzic ◽  
Thin Xuan Vo ◽  
Daniel B. Hardy ◽  
...  
Keyword(s):  
Growth Plate ◽  
Bone Growth ◽  
Long Bone ◽  
Tunel Staining ◽  
Long Bones ◽  
Micro Computed Tomography ◽  
Computed Tomography Scanning ◽  
Calcified Tissue ◽  
Trap Staining ◽  
Tomography Scanning

AbstractLongitudinal bone growth occurs through endochondral ossification (EO), controlled by various signaling molecules. Retinoid X Receptor (RXR) is a nuclear receptor with important roles in cell death, development, and metabolism. However, little is known about its role in EO. In this study, the agonist SR11237 was used to evaluate RXR activation on EO.Rats given SR11237 from post-natal day 5 to 15 were harvested for micro-computed tomography scanning and histology. In parallel, newborn CD1 mouse tibiae were cultured with increasing concentrations of SR11237 for histological and whole mount evaluation.RXR agonist-treated rats were smaller than controls, and developed dysmorphia of the growth plate. Cells invading the calcified and dysmorphic growth plate appeared pre-hypertrophic in size and shape corresponding with P57 immunostaining. Additionally, SOX9 positive cells were found surrounding the calcified tissue. The epiphysis of SR11237 treated bones showed increased TRAP staining, and additional TUNEL staining at the osteo-chondral junction. MicroCT revealed morphological disorganization in the long bones of treated animals. Isolated mouse long bones treated with SR11237 grew significantly less than their DMSO controls.This study demonstrates that stimulation of the RXR receptor causes irregular ossification, premature closure of the growth plate, and disrupted long bone growth in rodent models.

scholarly journals Integrated transcriptomics and metabolomics reveal signatures of lipid metabolism dysregulation in HepaRG liver cells exposed to PCB 126

2018 ◽  
Author(s):  
Robin Mesnage ◽  
Martina Biserni ◽  
Sucharitha Balu ◽  
Clément Frainay ◽  
Nathalie Poupin ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Fatty Liver ◽  
Polychlorinated Biphenyl ◽  
Expression Profiles ◽  
Human Populations ◽  
Limited Information ◽  
Chemical Pollutants ◽  
Pcb 126 ◽  
Heparg Cell Line ◽  
Chemical Pollutant

AbstractChemical pollutant exposure is a risk factor contributing to the growing epidemic of nonalcoholic fatty liver disease (NAFLD) affecting human populations that consume a Western diet. Although it is recognized that intoxication by chemical pollutants can lead to NAFLD, there is limited information available regarding the mechanism by which typical environmental levels of exposure can contribute to the onset of this disease. Here we describe the alterations in gene expression profiles and metabolite levels in the human hepatocyte HepaRG cell line, a validated model for cellular steatosis, exposed to the polychlorinated biphenyl (PCB) 126, one of the most potent chemical pollutants that can induce NAFLD. Sparse partial least squares classification of the molecular profiles revealed that exposure to PCB 126 provoked a decrease in polyunsaturated fatty acids as well as an increase in sphingolipid levels, concomitant with a decrease in the activity of genes involved in lipid metabolism. This was associated with an increased oxidative stress reflected by marked disturbances in taurine metabolism. A gene ontology analysis showed hallmarks of an activation of the AhR receptor by dioxin-like compounds. These changes in metabolome and transcriptome profiles were observed even at the lowest concentration (100 pM) of PCB 126 tested. A decrease in docosatrienoate levels was the most sensitive biomarker. Overall, our integrated multi-omics analysis provides mechanistic insight into how this class of chemical pollutant can cause NAFLD. Our study lays the foundation for the development of molecular signatures of toxic effects of chemicals causing fatty liver diseases to move away from a chemical risk assessment based on in vivo animal experiments.

scholarly journals Catch-Up Growth after Hypothyroidism Is Caused by Delayed Growth Plate Senescence

Endocrinology ◽  
2008 ◽  
Vol 149 (4) ◽  
pp. 1820-1828 ◽  
Author(s):  
Rose Marino ◽  
Anita Hegde ◽  
Kevin M. Barnes ◽  
Lenneke Schrier ◽  
Joyce A. Emons ◽  
...  
Keyword(s):  
Growth Rate ◽  
Growth Inhibition ◽  
Growth Plate ◽  
Bone Growth ◽  
Structural Characteristics ◽  
Linear Growth Rate ◽  
Growth Plate Chondrocytes ◽  
Growth Plates ◽  
Catch Up ◽  
Growth Inhibiting

Catch-up growth is defined as a linear growth rate greater than expected for age after a period of growth inhibition. We hypothesized that catch-up growth occurs because growth-inhibiting conditions conserve the limited proliferative capacity of growth plate chondrocytes, thus slowing the normal process of growth plate senescence. When the growth-inhibiting condition resolves, the growth plates are less senescent and therefore grow more rapidly than normal for age. To test this hypothesis, we administered propylthiouracil to newborn rats for 8 wk to induce hypothyroidism and then stopped the propylthiouracil to allow catch-up growth. In untreated controls, the growth plates underwent progressive, senescent changes in multiple functional and structural characteristics. We also identified genes that showed large changes in mRNA expression in growth plate and used these changes as molecular markers of senescence. In treated animals, after stopping propylthiouracil, these functional, structural, and molecular senescent changes were delayed, compared with controls. This delayed senescence included a delayed decline in longitudinal growth rate, resulting in catch-up growth. The findings demonstrate that growth inhibition due to hypothyroidism slows the developmental program of growth plate senescence, including the normal decline in the rate of longitudinal bone growth, thus accounting for catch-up growth.

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