The influence of bexarotene, a selective agonist of the retinoid receptor X (RXR), and tazarotene, a selective agonist of the retinoid acid receptor (RAR), on bone metabolism in rats

Nowak, Beata; Matuszewska, Agnieszka; Filipiak, Jarosław; Nikodem, Anna; Merwid-Ląd, Anna; Pieśniewska, Małgorzata; Fereniec-Gołębiewska, Lidia; Kwiatkowska, J; Szeląg, Adam

doi:10.1016/j.advms.2015.09.001

Cited by 7 publications

(7 citation statements)

References 23 publications

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“…It is also widely accepted that RXRs can modulate osteoclast and osteoblast formation, and function at several levels of cell differentiation and activation. For example, a previous study demonstrated that bexarotene, a selective agonist of RXRs, increased bone turnover in rats (66). On the other hand, Wang et al found that LPS inhibited RXR function and the reduction of its pathway-associated proteins (67).…”

Section: Discussionmentioning

confidence: 99%

lncRNA NEAT1 ameliorates LPS‑induced inflammation in MG63 cells by activating autophagy and suppressing the NLRP3 inflammasome

Dai

Wang

et al. 2020

Int J Mol Med

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The mechanisms of inflammation in bone and joint tissue are complex and involve long non-coding RNAs (lncRNAs), which play an important role in this process. The aim of the present study was to screen out differentially expressed genes in human osteoblasts stimulated by inflammation, and to further explore the mechanisms underlying inflammatory responses and the functional activity of human osteoblasts through bioinformatics methods and in vitro experiments. For this purpose, MG63 cells were stimulated with various concentrations of lipopolysaccharide (LPS) for different periods of time to construct an optimal inflammatory model and RNA sequencing was then performed on these cells. The levels of nuclear enriched abundant transcript 1 (NEAT1), various inflammatory factors, Nod-like receptor protein 3 (NLRP3) protein and osteogenesis-related proteins, as well as the levels of cell apoptosis- and cell cycle-related markers were measured in MG63 cells stimulated with LPS, transfected with NEAT1 overexpression plasmid and treated with bexarotene by western blot analysis, RT-qPCR, immunofluorescence, FISH, TEM and flow cytometry. There were 427 differentially expressed genes in the LPS-stimulated MG63 cells, in which NEAT1 was significantly downregulated. LPS upregulated the expression of inflammatory cytokines and NLRP3, inhibited the expression of autophagy-related and osteogenesis-related proteins, promoted apoptosis and altered the cell cycle, which was partially inhibited by NEAT1 overexpression and promoted by bexarotene. LPS stimulated inflammation in the MG63 cells and inhibited the retinoid X receptor (RXR)-α to downregulate the expression of NEAT1 and decrease levels of autophagy, which promoted the activation of NLRP3 and the release of inflammatory factors, and impaired the functional activity of osteoblasts, thus promoting the development of inflammation.

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Section: Discussionmentioning

confidence: 99%

lncRNA NEAT1 ameliorates LPS‑induced inflammation in MG63 cells by activating autophagy and suppressing the NLRP3 inflammasome

Dai

Wang

et al. 2020

Int J Mol Med

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“…By activating RXR specifically in the early newborn stage, prior to and during the onset of secondary ossification, using the RXR agonist SR11237, we found adverse effects on the growth plate of rat long bones, as well as effects on body size, bone formation, and morphology of multiple skeletal elements. Previous studies had examined the effects of other RXR agonists on bone parameters but were largely focused on adult stages [20]. Similarly, mice with specific deletions of the RXRα and RXRβ genes in hematopoietic cells showed defects in osteoclast function but were studied at later stages only [21].…”

Section: Discussionmentioning

confidence: 99%

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

Dupuis

Pest

Hadzic

et al. 2019

IJMS

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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

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“…The rst step stage was to determine the mechanical properties of rat tibiae in a trial of three-point bending. 23,31,32 This experimental study was conducted at the Department of Biomedical Engineering, Mechatronics and Theory of Mechanisms, Wroclaw University of Science and Technology.…”

Section: Bone Strength Analysismentioning

confidence: 99%

“…Impact of various external factors such as the discussed TCDD, 15,23 or drugs that prevent the development of skeletal diseases, affect the processes of bone remodeling. As the architecture of the bone tissue corresponds with its mechanical properties, examination of mechanical parameters enriches essentially the knowledge about the structure and functioning of bones [30][31][32] as well as it enables to dene the impact of the analyzed factors on the condition of bones.…”

Section: Introductionmentioning

confidence: 99%

Modulating effect of selected pharmaceuticals on bone in female rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

et al. 2018

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The influence of bexarotene, a selective agonist of the retinoid receptor X (RXR), and tazarotene, a selective agonist of the retinoid acid receptor (RAR), on bone metabolism in rats

Cited by 7 publications

References 23 publications

lncRNA NEAT1 ameliorates LPS‑induced inflammation in MG63 cells by activating autophagy and suppressing the NLRP3 inflammasome

lncRNA NEAT1 ameliorates LPS‑induced inflammation in MG63 cells by activating autophagy and suppressing the NLRP3 inflammasome

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

Modulating effect of selected pharmaceuticals on bone in female rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

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