scholarly journals Effects of hypothyroidism on the structure and mechanical properties of bone in the ovine fetus

2011 ◽  
Vol 210 (2) ◽  
pp. 189-198 ◽  
Author(s):  
S A Lanham ◽  
A L Fowden ◽  
C Roberts ◽  
C Cooper ◽  
R O C Oreffo ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Trabecular Bone ◽  
Growth And Development ◽  
Bone Growth ◽  
Bone Structure ◽  
Metatarsal Bone ◽  
Postnatal Life ◽  
Type I ◽  
Mineral Density

Thyroid hormones are important for normal bone growth and development in postnatal life. However, little is known about the role of thyroid hormones in the control of bone development in the fetus. Using computed tomography and mechanical testing, the structure and strength of metatarsal bones were measured in sheep fetuses in which thyroid hormone levels were altered by thyroidectomy or adrenalectomy. In intact fetuses, plasma concentrations of total calcium and the degradation products of C-terminal telopeptides of type I collagen increased between 100 and 144 days of gestation (term 145±2 days), in association with various indices of bone growth and development. Thyroid hormone deficiency induced by thyroidectomy at 105–110 days of gestation caused growth retardation of the fetus and significant changes in metatarsal bone structure and strength when analyzed at both 130 and 144 days of gestation. In hypothyroid fetuses, trabecular bone was stronger with thicker, more closely spaced trabeculae, despite lower bone mineral density. Plasma osteocalcin was reduced by fetal thyroidectomy. Removal of the fetal adrenal gland at 115–120 days of gestation, and prevention of the prepartum rises in cortisol and triiodothyronine, had no effect on bodyweight, limb lengths, metatarsal bone structure or strength, or circulating markers of bone metabolism in the fetuses studied near term. This study demonstrates that hypothyroidism in utero has significant effects on the structure and strength of bone, with different consequences for cortical and trabecular bone.

scholarly journals Bone Microarchitectural Changes in Hyperthyroid Women Compared to a Normal Canadian Cohort

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A256-A257
Author(s):  
Terra G Arnason ◽  
David Cooper ◽  
Reza Behdani ◽  
Saija Kontulainen
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Fracture Risk ◽  
Trabecular Bone ◽  
Bone Microarchitecture ◽  
Critical Role ◽  
Primary Objective ◽  
Mineral Density ◽  
Tsh Suppression ◽  
Increased Risk

Abstract Thyroid hormones play a critical role in bone physiology during childhood, but also impacts adult bone metabolism. Hyperthyroidism promotes accelerated bone turnover and bone remodelling which is associated with net loss of bone mineral density over time (BMD) and these changes have been quantitated using the gold standard of measuring BMD, Dual Energy X-ray Absorptiometry (DEXA). Ordinarily, biochemical thyroid hormone normalization restores BMD towards normal, yet an increased risk of fractures remains lifelong. DEXA, therefore, cannot explain the underlying etiology for fracture risk which may be due to undetected changes in bone microarchitecture. Our primary objective was to utilize an investigational 3-dimensional bone imaging technology, High Resolution peripheral Quantitative Tomography (HR-pQCT), to study bone microarchitecture in actively hyperthyroid women to determine if there are changes in cortical and trabecular bone microarchitecture from that of age-matched controls. A subset of women were rescanned using HR-pCT after thyroid hormones had been normalized for at least 6 months to determine if there were cortical/trabecular architectural changes that reversed towards normal in these individual cases. We enrolled 20 hyperthyroid women (age 20–76) for this pilot study who had persistent TSH suppression for >3 months (TSH< 0.5, normal range: 0.5–4.49 mU/L) without secondary causes for bone loss. Their etiology was divided amongst TSH suppression for thyroid carcinoma, Grave’s disease and iatrogenic hyperthyroidism. HR-pQCT scans of the radius were compared to age-matched scans of normal females, available from the robust Canadian Multicentre Osteoporosis Study (CaMOS) control cohort. Four participants were re-scanned after 6 months of TSH normalization to assess reversibility. The observed data showed statistically significant differences in key parameters of bone microarchitecture in hyperthyroidism, independent of etiology. We observed decreased cortical thickness and increased failure load as statistically different from age-matched controls. Increases in cortical bone porosity and decreases in volumetric bone density (cortical, trabecular and total) were notable but did not reach significance in this small study. Repeat scans following normalization of thyroid hormone levels revealed consistent (partial, nonsignificant) normalization of multiple bone microarchitecture elements including increased trabecular number/thickness, and decreased cortical porosity. These findings suggest that there are changes in both cortical and trabecular bone during active hyperthyroidism that may contribute to increased lifelong fracture risk.

Regulation of Mammary Gland Sensitivity to Thyroid Hormones During the Transition from Pregnancy to Lactation

2008 ◽  
Vol 233 (10) ◽  
pp. 1309-1314 ◽  
Author(s):  
A. V. Capuco ◽  
E. E. Connor ◽  
D. L. Wood
Keyword(s):  
Mammary Gland ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Thyroid Hormone Receptor ◽  
Physiological State ◽  
Expression Patterns ◽  
Type I ◽  
Hormone Activity ◽  
Iodothyronine Deiodinase ◽  
Copy Numbers

Thyroid hormones are galactopoietic and help to establish the mammary gland’s metabolic priority during lactation. Expression patterns for genes that can alter tissue sensitivity to thyroid hormones and thyroid hormone activity were evaluated in the mammary gland and liver of cows at 53, 35, 20, and 7 days before expected parturition, and 14 and 90 days into the subsequent lactation. Transcript abundance for the three isoforms of iodothyronine deiodinase, type I ( DIO1), type II ( DIO2) and type III ( DIO3), thyroid hormone receptors alpha1 ( TRα 1), alpha2 ( TRα 2) and beta1 ( TRβ 1), and retinoic acid receptors alpha ( RXRα) and gamma ( RXRγ), which act as coregulators of thyroid hormone receptor action, were evaluated by quantitative RT-PCR. The DIO3 is a 5-deiodinase that produces inactive iodothyronine metabolites, whereas DIO1 and DIO2 generate the active thyroid hormone, triiodothyronine, from the relatively inactive precursor, thyroxine. Low copy numbers of DIO3 transcripts were present in mammary gland and liver. DIO2 was the predominant isoform expressed in mammary gland and DIO1 was the predominant isoform expressed in liver. Quantity of DIO1 mRNA in liver tissues did not differ with physiological state, but tended to be lowest during lactation. Quantity of DIO2 mRNA in mammary gland increased during lactation ( P < 0.05), with copy numbers at 90 days of lactation 6-fold greater than at 35 and 20 days prepartum. When ratios of DIO2/DIO3 mRNA were evaluated, the increase was more pronounced (>100-fold). Quantity of TRβ 1 mRNA in mammary gland increased with onset of lactation, whereas TRα 1 and TRα 2 transcripts did not vary with physiological state. Conversely, quantity of RXRα mRNA decreased during late gestation to low levels during early lactation. Data suggest that increased expression of mammary TRβ 1 and DIO2, and decreased RXRα, provide a mechanism to increase thyroid hormone activity within the mammary gland during lactation.

scholarly journals Anabolic Actions of Parathyroid Hormone during Bone Growth Are Dependent on c-fos

Endocrinology ◽  
2002 ◽  
Vol 143 (10) ◽  
pp. 4038-4047 ◽  
Author(s):  
Burak Demiralp ◽  
Hen-Li Chen ◽  
Amy J. Koh ◽  
Evan T. Keller ◽  
Laurie K. McCauley
Keyword(s):  
Trabecular Bone ◽  
Mrna Expression ◽  
Bone Growth ◽  
Critical Role ◽  
Calcium Content ◽  
Wild Type ◽  
Mineral Density ◽  
Femoral Bone Mineral Density ◽  
Endochondral Bone ◽  
Ash Weight

Abstract PTH has anabolic and catabolic actions in bone that are not clearly understood. The protooncogene c-fos and other activating protein 1 family members are critical transcriptional mediators in bone, and c-fos is up-regulated by PTH. The purpose of this study was to examine the mechanisms of PTH and the role of c-fos in PTH-mediated anabolic actions in bone. Mice with ablation of c-fos (−/−) and their wild-type (+/+) and heterozygous (+/−) littermates were administered PTH for 17 d. The +/+ mice had increased femoral bone mineral density (BMD), whereas −/− mice had reduced BMD after PTH treatment. PTH increased the ash weight of +/+ and +/−, but not −/−, femurs and decreased the calcium content of −/−, but not +/+ or +/−, femurs. Histomorphometric analysis showed that PTH increased trabecular bone volume in c-fos +/+, +/− vertebrae, but, in contrast, decreased trabecular bone in −/− vertebrae. Serum calcium levels in +/+ mice were greater than those in −/− mice, and PTH increased calcium in −/− mice. Histologically, PTH resulted in an exacerbation of the already widened growth plate and zone of hypertrophic chondrocytes but not the proliferating zone in −/− mice. PTH also increased calvarial thickness in +/+ mice, but not −/− mice. The c-fos −/− mice had lower bone sialoprotein and osteocalcin (OCN), but unaltered PTH-1 receptor mRNA expression in calvaria, suggesting an alteration in extracellular matrix. Acute PTH injection (8 h) resulted in a decrease in osteocalcin mRNA expression in wild-type, but unaltered expression in −/−, calvaria. These data indicate that c-fos plays a critical role in the anabolic actions of PTH during endochondral bone growth.

Bone and muscle development in three inbred female mouse strains

2021 ◽  
Author(s):  
Ursula Föger-Samwald ◽  
Maria Papageorgiou ◽  
Katharina Wahl-Figlash ◽  
Katharina Kerschan-Schindl ◽  
Peter Pietschmann
Keyword(s):  
Trabecular Bone ◽  
Muscle Development ◽  
Bone Growth ◽  
Volume Fraction ◽  
Bone Structure ◽  
Bone Development ◽  
Mouse Strains ◽  
Structural Reorganization ◽  
Bone Volume Fraction ◽  
Trabecular Thickness

AbstractMuscle force is thought to be one of the main determinants of bone development. Hence, peak muscle growth is expected to precede peak bone growth. In this study, we investigated muscle and bone development in female C57BL/6 J, DBA/2JRj, and C3H/HeOuJ mice. Femoral cortical and trabecular bone structure and the weights of selected muscles were assessed at the ages of 8, 16, and 24 weeks. Muscle mass increased from 8 to 24 weeks in all 3 strains, suggesting peak muscle development at 24 weeks or later. Bone volume fraction, trabecular number, and connectivity density of the femur decreased or remained unchanged, whereas trabecular density and trabecular thickness largely increased. These results suggest a peak in trabecular bone accrual at 8 weeks or earlier followed by further increases in density and structural reorganization of trabeculae. Cortical density, cortical thickness, and cortical cross sectional area increased over time, suggesting a peak in cortical bone accrual at 24 weeks or later. In conclusion, our data provide evidence that growth of muscle lags behind trabecular bone accrual.

scholarly journals Zhuang-Gu-Fang Treats Osteoporosis in Ovariectomized Rats by Increasing the Osteogenesis-Related Factors Leptin, Ghrelin, and PYY

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yuanjin Chen ◽  
Rui Bai ◽  
Wenhui Chen ◽  
Shuanglei Li ◽  
Yunxia Jiang
Keyword(s):  
Bone Metabolism ◽  
Therapeutic Effect ◽  
Wistar Rats ◽  
Dose Group ◽  
Bone Structure ◽  
Ovariectomized Rats ◽  
Type I ◽  
Mineral Density ◽  
Related Factors ◽  
Expression Levels

Zhuang-Gu-Fang is a Chinese medicinal compound mixture, which is mainly composed of traditional remedies like the Epimedium Herb, Astragalus, and Eucommia among many others. The study is aimed at investigating the therapeutic effect of Zhuang-Gu-Fang in ovariectomized rats. Fifty six-month-old Wistar rats were randomly selected and divided into 5 groups (n = 10), namely, model group, positive group, low-dose Chinese medicine group, medium-dose group, and high-dose group. Another 10 sham operation Wistar rats were taken as a negative control group. After 3 months of intervention, the bone mineral density (BMD), procollagen type I N-peptide (PINP), beta C-terminal cross-linked telopeptides of type I collagen carboxyl-terminal peptide (β-CTX), Leptin, Ghrelin, and Peptide YY (PYY) of each group were measured. Besides, the ultrastructure of bone structure and osteoblasts was also observed by transmission electron microscopy. Western blot method was used to detect the expression levels of Leptin and Ghrelin in bone tissue, and RT-PCR detected the mRNA expression levels of Leptin and Ghrelin. BMD test indicated that Zhuang-Gu-Fang could effectively prevent the loss of tibia bone in ovariectomized rats. Histomorphology analysis showed that Zhuang-Gu-Fang could preserve trabecular bone structure integrity and improve osteoblast ultrastructure. Notably, the study found out that Zhuang-Gu-Fang worked through balancing the bone metabolism via increasing bone formation/resorption ratio. Additionally, Zhuang-Gu-Fang highlighted the recovery effects in multiple levels of osteogenesis- and osteanagenesis-related factors Leptin, Ghrelin, and PYY. Conclusively, the study proved the therapeutic potential of the Zhuang-Gu-Fang for postmenopausal osteoporosis (PMOP) and further revealed that its therapeutic effect was related to the balance of bone metabolism and the recovery effects of bone-related factors Leptin, Ghrelin, and PYY.

scholarly journals Sex- and bone-specific responses in bone structure to exogenous leptin and leptin receptor antagonism in the ovine fetus

2018 ◽  
Vol 314 (6) ◽  
pp. R781-R790 ◽  
Author(s):  
Miles J. De Blasio ◽  
Stuart A. Lanham ◽  
Dominique Blache ◽  
Richard O. C. Oreffo ◽  
Abigail L. Fowden ◽  
...  
Keyword(s):  
Growth And Development ◽  
Bone Growth ◽  
Leptin Receptor ◽  
Bone Structure ◽  
Lumbar Vertebrae ◽  
Late Gestation ◽  
Trabecular Thickness ◽  
Receptor Antagonism ◽  
Treatment Groups ◽  
Ovine Fetus

Widespread expression of leptin and its receptor in developing cartilage and bone suggests that leptin may regulate bone growth and development in the fetus. Using microcomputed tomography, this study investigated the effects of exogenous leptin and leptin receptor antagonism on aspects of bone structure in the sheep fetus during late gestation. From 125 to 130 days of gestation (term ~145 days), chronically catheterized singleton sheep fetuses were infused intravenously for 5 days with either saline (0.9% saline, n = 13), recombinant ovine leptin at two doses (0.6 mg·kg−1·day−1 LEP1, n = 10 or 1.4 mg·kg−1·day−1 LEP2, n = 7), or recombinant superactive ovine leptin receptor antagonist (4.6 mg·kg−1·day−1 SOLA, n = 6). No significant differences in plasma insulin-like growth factor-I, osteocalcin, calcium, inorganic phosphate, or alkaline phosphatase were observed between treatment groups. Total femur midshaft diameter and metatarsal lumen diameter were narrower in male fetuses treated with exogenous leptin. In a fixed length of femur midshaft, total and bone volumes were reduced by the higher dose of leptin; nonbone space volume was lower in both groups of leptin-treated fetuses. Leptin infusion caused increments in femur porosity and connectivity density, and vertebral trabecular thickness. Leptin receptor antagonism decreased trabecular spacing and increased trabecular number, degree of anisotrophy, and connectivity density in the lumbar vertebrae. The increase in vertebral porosity observed following leptin receptor antagonism was greater in the malecompared with female, fetuses. Therefore, leptin may have a role in the growth and development of the fetal skeleton, dependent on the concentration of leptin, sex of the fetus, and bone type examined.

scholarly journals Athyroid Pax8−/− Mice Cannot Be Rescued by the Inactivation of Thyroid Hormone Receptor α1

Endocrinology ◽  
2005 ◽  
Vol 146 (7) ◽  
pp. 3179-3184 ◽  
Author(s):  
Jens Mittag ◽  
Sönke Friedrichsen ◽  
Heike Heuer ◽  
Silke Polsfuss ◽  
Theo J. Visser ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Postnatal Life ◽  
Mrna Levels ◽  
Negative Effects ◽  
Double Knockout ◽  
Short Life Span ◽  
Knockout Animals

Abstract The Pax8−/− mouse provides an ideal animal model to study the consequences of congenital hypothyroidism, because its only known defect is the absence of thyroid follicular cells. Pax8−/− mice are, therefore, completely athyroid in postnatal life and die around weaning unless they are substituted with thyroid hormones. As reported recently, Pax8−/− mice can also be rescued and survive to adulthood by the additional elimination of the entire thyroid hormone receptor α (TRα) gene, yielding Pax8−/−TRαo/o double-knockout animals. This observation has led to the hypothesis that unliganded TRα1 might be responsible for the lethal phenotype observed in Pax8−/− animals. In this study we report the generation of Pax8−/−TRα1−/− double-knockout mice that still express the non-T3-binding TR isoforms α2 and Δα2. These animals closely resemble the phenotype of Pax8−/− mice, including growth retardation and a completely distorted appearance of the pituitary with thyrotroph hyperplasia and hypertrophy, extremely high TSH mRNA levels, reduced GH mRNA expression, and the almost complete absence of lactotrophs. Like Pax8−/− mice, Pax8−/−TRα1−/− compound mutants die around weaning unless they are substituted with thyroid hormones. These findings do not support the previous interpretation that the short life span of Pax8−/− mice is due to the negative effects of the TRα1 aporeceptor, but, rather, suggest a more complex mechanism involving TRα2 and an unliganded TR isoform.

IL-1RI participates in normal growth plate development and bone modeling

2013 ◽  
Vol 305 (1) ◽  
pp. E15-E21 ◽  
Author(s):  
Stav Simsa-Maziel ◽  
Janna Zaretsky ◽  
Adi Reich ◽  
Yoav Koren ◽  
Ron Shahar ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Growth Plate ◽  
Knockout Mice ◽  
Bone Structure ◽  
Interleukin 1 ◽  
Normal Growth ◽  
Bone Modeling ◽  
Type I ◽  
Mineral Density ◽  
Plate Morphology

The proinflammatory cytokine interleukin-1 (IL-1) signals through IL-1 receptor type I (IL-1RI) and induces osteoclastogenesis and bone resorption mainly during pathological conditions. Little is known about the effect of excess or absence of IL-1 signaling on the physiological development of the growth plate and bone. In this study, we examine growth plate morphology, bone structure, and mechanical properties as well as osteoclast number in IL-1RI knockout mice to evaluate the role of IL-1RI in the normal development of the growth plate and bone. We show for the first time that IL-1RI knockout mice have narrower growth plates due to a smaller hypertrophic zone, suggesting a role for this cytokine in hypertrophic differentiation, together with higher proteoglycan content. The bones of theses mice exhibit higher trabecular and cortical mass, increased mineral density, and superior mechanical properties. In addition, IL-1RI knockout mice have significantly reduced osteoclast numbers in the chondro-osseous junction, trabecular bone, and cortical bone. These results suggest that IL-1RI is involved in normal growth plate development and ECM homeostasis and that it is significant in the physiological process of bone modeling.

scholarly journals SAT-395 Correlations Between Biochemical Parameters and Trabecular Bone Score (TBS) in Primary Hyperparathyroidism (PHP) Patients

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Lívia Marcela Santos ◽  
Monique Nakayama Ohe ◽  
Sthefanie Giovanna Pallone ◽  
Ilda Sizue Kunii ◽  
Renata Elen Costa Silva ◽  
...  
Keyword(s):  
Vitamin D ◽  
Trabecular Bone ◽  
Vitamin D Deficiency ◽  
Negative Correlation ◽  
Bone Structure ◽  
Trabecular Bone Score ◽  
Control Group ◽  
Total Calcium ◽  
Mineral Density ◽  
Positive Correlation

Abstract Background: Vitamin D deficiency is common among PHP patients. While data are limited, some studies suggest that vitamin D deficiency may exacerbates skeletal disease in PHP. TBS is a software-based method for assessment of trabecular bone structure of the spine, based on analysis of pixels obtained in dual energy x-ray absorptiometry (DXA) images. The aim of this study was to evaluate TBS, vitamin D status, clinical and laboratorial measurements in a PHP group of patients in a search for a more accurate bone fragility test for risk assessment in this group of patients. Methods: From June/2017 to January/2019, patients who met the criteria for PHP diagnosis were included in this study. Control group was composed by age and sex-matched healthy individuals. Overall, 64 PHP and 63 controls were enrolled. Bone mineral density (BMD) measured by DXA (Hologic QDR 4500) at the lumbar spine, total hip, femoral neck, and TBS values (InSight™) were determined in both groups. Total and ionized calcium, PTH, 25-hydroxyvitamin D (25(OH)D), creatinine, alkaline phosphatase, P1NP and CTX were measured. None were in use of Vitamin D supplementation. Results: As expected, PHP patients had lower BMD values than controls in all sites (p&lt;0.0001). TBS measurements were also reduced in PHP patients compared to controls (1233 vs 1280, p=0.0444). TBS values were inversely correlated with total calcium (CaT) and phosphorus measurements were positively correlated in the PHP patients. 25(OH)D measurements didn’t differ between groups (PHP 22.5 vs. controls 19.8 ng/mL, p=0.1699). There was a positive correlation between 25(OH)D and TBS in both PHP and controls (r= 0,3088, p= 0,0138 and r= 0,3708, p= 0,003 respectively). Considering individuals with vitamin D deficiency (25(OH)D levels &lt;=20 ng/mL), a negative correlation between TBS and CaT measurements among PHP patients (r= -0,4391, p=0,0172) was observeed, while in controls there was a positive correlation between TBS and 25(OH)D (r= 0,3504, p= 0,0362). Conclusion: Serum total calcium presents negative correlation and phosphorus a positive one with TBS in PHP patients. We also found a correlation between TBS and 25(OH)D, both in PHP and in controls. 25(OH)D &lt;=20 ng/mL is an independent risk factor determining degraded TBS among PHP patients and controls.

scholarly journals The Role of Omega-3 Polyunsaturated Fatty Acids from Different Sources in Bone Development

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3494
Author(s):  
Reut Rozner ◽  
Janna Vernikov ◽  
Shelley Griess-Fishheimer ◽  
Tamar Travinsky ◽  
Svetlana Penn ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Trabecular Bone ◽  
Molecular Mechanisms ◽  
Bone Structure ◽  
Bone Development ◽  
Bending Test ◽  
Mineral Density ◽  
Different Sources

N-3 polyunsaturated fatty acids (PUFAs) are essential nutrients that must be obtained from the diet. We have previously showed that endogenous n-3 PUFAs contribute to skeletal development and bone quality in fat-1 mice. Unlike other mammals, these transgenic mice, carry the n-3 desaturase gene and thus can convert n-6 to n-3 PUFAs endogenously. Since this model does not mimic dietary exposure to n-3 PUFAs, diets rich in fish and flaxseed oils were used to further elucidate the role of n-3 PUFAs in bone development. Our investigation reveals that dietary n-3 PUFAs decrease fat accumulation in the liver, lower serum fat levels, and alter fatty acid (FA) content in liver and serum. Bone analyses show that n-3 PUFAs improve mechanical properties, which were measured using a three-point bending test, but exert complex effects on bone structure that vary according to its source. In a micro-CT analysis, we found that the flaxseed oil diet improves trabecular bone micro-architecture, whereas the fish oil diet promotes higher bone mineral density (BMD) with no effect on trabecular bone. The transcriptome characterization of bone by RNA-seq identified regulatory mechanisms of n-3 PUFAs via modulation of the cell cycle and peripheral circadian rhythm genes. These results extend our knowledge and provide insights into the molecular mechanisms of bone remodeling regulation induced by different sources of dietary n-3 PUFAs.

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