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 Exposure to the RXR Agonist SR11237 in Early Life Causes Disturbed Skeletal Morphogenesis in a Rat Model

2019 ◽  
Vol 20 (20) ◽  
pp. 5198
Author(s):  
Holly Dupuis ◽  
Michael Andrew Pest ◽  
Ermina Hadzic ◽  
Thin Xuan Vo ◽  
Daniel B. Hardy ◽  
...  
Keyword(s):  
Growth Plate ◽  
Endochondral Ossification ◽  
Bone Growth ◽  
Long Bone ◽  
Tunel Staining ◽  
Long Bones ◽  
Micro Computed Tomography ◽  
Calcified Tissue ◽  
Trap Staining ◽  
Stimulation Of

Longitudinal 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 in EO. Rats given SR11237 from post-natal day 5 to post-natal day 15 were harvested for micro-computed tomography (microCT) 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 had shorter long bones than the controls and developed dysmorphia of the growth plate. Cells invading the calcified and dysmorphic growth plate appeared pre-hypertrophic in size and shape, in correspondence 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 the treated animals. This study suggests that stimulation of RXR causes irregular ossification, premature closure of the growth plate, and disrupted long bone growth in rodent models

Longitudinal bone growth in vitro: effects of insulin-like growth factor I and growth hormone

1991 ◽  
Vol 124 (5) ◽  
pp. 602-607 ◽  
Author(s):  
Ben A. A. Scheven ◽  
Nicola J. Hamilton
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Bone Growth ◽  
Long Bone ◽  
Long Bones ◽  
Insulin Like Growth Factor ◽  
Serum Free ◽  
Factor I ◽  
Igf I

Abstract. Longitudinal growth was studied using an in vitro model system of intact rat long bones. Metatarsal bones from 18- and 19-day-old rat fetuses, entirely (18 days) or mainly (19 days) composed of chondrocytes, showed a steady rate of growth and radiolabelled thymidine incorporation for at least 7 days in serum-free media. Addition of recombinant human insulin-like growth factor-I to the culture media resulted in a direct stimulation of the longitudinal growth. Recombinant human growth hormone was also able to stimulate bone growth, although this was generally accomplished after a time lag of more than 2 days. A monoclonal antibody to IGF-I abolished both the IGF-I and GH-stimulated growth. However, the antibody had no effect on the growth of the bone explants in control, serum-free medium. Unlike the fetal long bones, bones from 2-day-old neonatal rats were arrested in their growth after 1-2 days in vitro. The neonatal bones responded to IGF-I and GH in a similar fashion as the fetal bones. Thus in this study in vitro evidence of a direct effect of GH on long bone growth via stimulating local production of IGF by the growth plate chondrocytes is presented. Furthermore, endogenous growth factors, others than IGFs, appear to play a crucial role in the regulation of fetal long bone growth.

scholarly journals Repeated irradiation from micro-computed tomography scanning at 2, 4 and 6 months of age does not induce damage to tibial bone microstructure in male and female CD-1 mice

2017 ◽  
Vol 6 ◽  
pp. 855 ◽  
Author(s):  
Sandra M Sacco ◽  
Caitlin Saint ◽  
Amanda B Longo ◽  
Charles B Wakefield ◽  
Phil L Salmon ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Bone Microstructure ◽  
Micro Computed Tomography ◽  
Male And Female ◽  
Tibial Bone ◽  
Computed Tomography Scanning ◽  
Tomography Scanning

A novel approach for computing 3D mice distal femur properties using high-resolution micro-computed tomography scanning

Micron ◽  
2019 ◽  
Vol 121 ◽  
pp. 1-7 ◽  
Author(s):  
Brahim Mehadji ◽  
Yoseph Ahmed ◽  
Jean-Philippe Berteau
Keyword(s):  
Computed Tomography ◽  
High Resolution ◽  
Distal Femur ◽  
Micro Computed Tomography ◽  
Novel Approach ◽  
Computed Tomography Scanning ◽  
Tomography Scanning

scholarly journals Inner histopathologic changes and disproportionate zone volumes in foetal growth plates following gestational hypoglycaemia in rats

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Vivi F. H. Jensen ◽  
Anne-Marie Mølck ◽  
Ingrid B. Bøgh ◽  
Jette Nowak ◽  
Birgitte M. Viuff ◽  
...  
Keyword(s):  
Growth Plate ◽  
Bone Growth ◽  
Skeletal Development ◽  
Long Bone ◽  
Structural Protein ◽  
Pregnant Rats ◽  
Growth Plates ◽  
Chondrocyte Maturation ◽  
Foetal Growth ◽  
Histopathologic Changes

AbstractMaternal hypoglycaemia throughout gestation until gestation day (GD)20 delays foetal growth and skeletal development. While partially prevented by return to normoglycaemia after completed organogenesis (GD17), underlying mechanisms are not fully understood. Here, we investigated the pathogenesis of these changes and significance of maternal hypoglycaemia extending beyond organogenesis in non-diabetic rats. Pregnant rats received insulin-infusion until GD20 or GD17, with sacrifice on GD20. Hypoglycaemia throughout gestation increased maternal corticosterone levels, which correlated with foetal levels. Growth plates displayed central histopathologic changes comprising disrupted cellular organisation, hypertrophic chondrocytes, and decreased cellular density; expression of pro-angiogenic factors, HIF-1α and VEGF-A increased in surrounding areas. Disproportionately decreased growth plate zone volumes and lower expression of the structural protein MATN-3 were seen, while bone ossification parameters were normal. Ending maternal/foetal hypoglycaemia on GD17 reduced incidence and severity of histopathologic changes and with normal growth plate volume. Compromised foetal skeletal development following maternal hypoglycaemia throughout gestation is hypothesised to result from corticosterone-induced hypoxia in growth plates, where hypoxia disrupts chondrocyte maturation and growth plate structure and volume, decreasing long bone growth. Maternal/foetal hypoglycaemia lasting only until GD17 attenuated these changes, suggesting a pivotal role of glucose in growth plate development.

Ontogenetic development of the otic region in the new model organism, Leucoraja erinacea (Chondrichthyes; Rajidae)

2018 ◽  
Vol 109 (1-2) ◽  
pp. 105-114 ◽  
Author(s):  
Cathrin PFAFF ◽  
Jürgen KRIWET ◽  
Kyle MARTIN ◽  
Zerina JOHANSON
Keyword(s):  
Soft Tissues ◽  
Developmental Stages ◽  
Model Organism ◽  
Model Organisms ◽  
Biological Research ◽  
Developmental Studies ◽  
Micro Computed Tomography ◽  
Computed Tomography Scanning ◽  
Cartilaginous Fishes ◽  
Tomography Scanning

ABSTRACTCartilaginous fishes have a long evolutionary history dating back 440 million years and include model organisms in a number of fields of biological research. However, comparative developmental studies of these organisms, particularly neuroanatomical investigations, still remain sparse. Here, pre-hatching to adult developmental stages of the Little Skate, Leucoraja erinacea, are investigated using micro-computed tomography scanning in conjunction with staining procedures designed to improve visualisation of soft tissues. Within the ear, the anatomy of the skeletal labyrinth changes during ontogeny and differs substantially from the underlying membranous system, contrary to previous observations in sharks. Additionally, substantial morphological remodelling characterises the parietal fossa, which appears initially as a massive and hook-like structure and subsequently becomes slender and surrounded by soft tissue. The sizes of the vestibular system and neurocranium increase isometrically from pre- to post-hatching phases, and then exponentially after the post-hatching stages.

scholarly journals Analysis of short-term treatment with the phosphodiesterase type 5 inhibitor tadalafil on long bone development in young rats

2018 ◽  
Vol 315 (4) ◽  
pp. E446-E453 ◽  
Author(s):  
Luqiang Wang ◽  
Haoruo Jia ◽  
Robert J. Tower ◽  
Michael A. Levine ◽  
Ling Qin
Keyword(s):  
Growth Plate ◽  
Time Course ◽  
Bone Growth ◽  
Bone Structure ◽  
Primary Cultures ◽  
Long Bone ◽  
Short Term ◽  
Short Term Treatment ◽  
Bone Properties ◽  
Phosphodiesterase Type 5 Inhibitor

Cyclic GMP (cGMP) is an important intracellular regulator of endochondral bone growth and skeletal remodeling. Tadalafil, an inhibitor of the phosphodiesterase (PDE) type 5 (PDE5) that specifically hydrolyzes cGMP, is increasingly used to treat children with pulmonary arterial hypertension (PAH), but the effect of tadalafil on bone growth and strength has not been previously investigated. In this study, we first analyzed the expression of transcripts encoding PDEs in primary cultures of chondrocytes from newborn rat epiphyses. We detected robust expression of PDE5 as the major phosphodiesterase hydrolyzing cGMP. Time-course experiments showed that C-type natriuretic peptide increased intracellular levels of cGMP in primary chondrocytes with a peak at 2 min, and in the presence of tadalafil the peak level of intracellular cGMP was 37% greater ( P < 0.01) and the decline was significantly attenuated. Next, we treated 1-mo-old Sprague Dawley rats with vehicle or tadalafil for 3 wk. Although 10 mg·kg−1·day−1 tadalafil led to a significant 52% ( P < 0.01) increase in tissue levels of cGMP and a 9% reduction ( P < 0.01) in bodyweight gain, it did not alter long bone length, cortical or trabecular bone properties, and histological features. In conclusion, our results indicate that PDE5 is highly expressed in growth plate chondrocytes, and short-term tadalafil treatment of growing rats at doses comparable to those used in children with PAH has neither obvious beneficial effect on long bone growth nor any observable adverse effect on growth plate structure and trabecular and cortical bone structure.

scholarly journals Beam hardening artifacts in micro-computed tomography scanning can be reduced by X-ray beam filtration and the resulting images can be used to accurately measure BMD

Bone ◽  
2009 ◽  
Vol 45 (6) ◽  
pp. 1104-1116 ◽  
Author(s):  
Jeffrey A. Meganck ◽  
Kenneth M. Kozloff ◽  
Michael M. Thornton ◽  
Stephen M. Broski ◽  
Steven A. Goldstein
Keyword(s):  
Computed Tomography ◽  
Micro Computed Tomography ◽  
Beam Hardening ◽  
X Ray ◽  
Computed Tomography Scanning ◽  
Tomography Scanning

scholarly journals Estrogen stimulates leptin receptor expression in ATDC5 cells via the estrogen receptor and extracellular signal-regulated kinase pathways

2012 ◽  
Vol 213 (2) ◽  
pp. 163-172 ◽  
Author(s):  
Shan-Jin Wang ◽  
Xin-Feng Li ◽  
Lei-Sheng Jiang ◽  
Li-Yang Dai
Keyword(s):  
Growth Plate ◽  
Cross Talk ◽  
Bone Growth ◽  
Leptin Receptor ◽  
Receptor Expression ◽  
Long Bone ◽  
Endochondral Bone Formation ◽  
Dependent Manner ◽  
Growth Plate Chondrocytes ◽  
Concentration Dependent Manner

Regulation of the physiological processes of endochondral bone formation during long bone growth is controlled by various factors including the hormones estrogen and leptin. The effects of estrogen are mediated not only through the direct activity of estrogen receptors (ERs) but also through cross talk with other signaling systems implicated in chondrogenesis. The receptors of both estrogen and leptin (OBR (LEPR)) are detectable in growth plate chondrocytes of all zones. In this study, the expression of mRNA and protein of OBR in chondrogenic ATDC5 cells and the effect of 17β-estradiol (E2) stimulation were assessed using quantitative PCR and western blotting. We have found that the mRNA of Obr was dynamically expressed during the differentiation of ATDC5 cells over 21 days. Application of E2 (10−7 M) at day 14 for 48 h significantly upregulated OBR mRNA and protein levels (P<0.05). The upregulation of Obr mRNA by E2 was shown to take place in a concentration-dependent manner, with a concentration of 10−7 M E2 having the greatest effect. Furthermore, we have confirmed that E2 affected the phosphorylation of ERK1/2 (MAPK1/MAPK3) in a time-dependent manner where a maximal fourfold change was observed at 10 min following application of E2. Finally, pretreatment of the cells with either U0126 (ERK1/2 inhibitor) or ICI 182 780 (ER antagonist) blocked the upregulation of OBR by E2 and prevented the E2-induced phosphorylation of ERK. These data demonstrate, for the first time, the existence of cross talk between estrogen and OBR in the regulation of bone growth whereby estrogen regulates the expression of Obr in growth plate chondrocytes via ERs and the activation of ERK1/2 signaling pathways.

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