Estradiol-induced RORα expression positively regulates osteoblast differentiation

Min, Hyeon-Young; Son, Hyo-Eun; Jang, Won‐Gu

doi:10.1016/j.steroids.2019.05.004

Cited by 12 publications

(9 citation statements)

References 27 publications

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“…RORα also mediates the role of melatonin in regulating hair growth and reducing neuropathic pain [ 45 , 46 , 47 ]. Both melatonin and RORα are associated with the regulation of bone and lipid metabolism, insulin secretion, and glucose tolerance; however, it is difficult to determine whether their effects are related [ 5 , 48 , 49 ].…”

Section: Expression and Functions Of Retinoic Acid-related Orphan Receptormentioning

confidence: 99%

“…Functionally, many studies have suggested that melatonin and ROR have identical functions [ 5 , 40 , 48 , 52 , 54 , 63 , 64 ], and that ROR mediates a number of melatonin functions [ 27 , 28 , 29 , 30 , 35 , 36 , 37 , 38 , 39 , 40 ]. Moreover, melatonin is found to exert an additional effect on the transcription of target genes of ROR, as reported by studies covering a wide range of areas, including immune regulation, inflammation suppression, oxidative stress, circadian rhythms, tumour development, reproduction, hair growth, bone metabolism, and lipid metabolism.…”

Section: Retinoic Acid-related Orphan Receptor and Melatonin: Direct Binding Or Indirect Modulation?mentioning

confidence: 99%

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ROR: Nuclear Receptor for Melatonin or Not?

Kang

Fan

et al. 2021

Molecules

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Whether the retinoic acid-related orphan receptor (ROR) is a nuclear receptor of melatonin remains controversial. ROR is inextricably linked to melatonin in terms of its expression, function, and mechanism of action. Additionally, studies have illustrated that melatonin functions analogous to ROR ligands, thereby modulating the transcriptional activity of ROR. However, studies supporting these interactions have since been withdrawn. Furthermore, recent crystallographic evidence does not support the view that ROR is a nuclear receptor of melatonin. Some other studies have proposed that melatonin indirectly regulates ROR activity rather than directly binding to ROR. This review aims to delve into the complex relationship of the ROR receptor with melatonin in terms of its structure, expression, function, and mechanism. Thus, we provide the latest evidence and views on direct binding as well as indirect regulation of ROR by melatonin, dissecting both viewpoints in-depth to provide a more comprehensive perspective on this issue.

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Section: Expression and Functions Of Retinoic Acid-related Orphan Receptormentioning

confidence: 99%

Section: Retinoic Acid-related Orphan Receptor and Melatonin: Direct Binding Or Indirect Modulation?mentioning

confidence: 99%

ROR: Nuclear Receptor for Melatonin or Not?

Kang

Fan

et al. 2021

Molecules

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“…After quantifying total protein according to the previously reported method, protein samples were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred to a polyvinylidene fluoride membrane. 13,22 Signals were detected using ECL reagent (Advansta, Menlo Park, CA, USA) according to the manufacturer's protocol. Densitometric analysis of the blotted membrane was performed using a Fusion Solo system (Vilber Lourmat, Eberhardzell, Germany).…”

Section: Western Blottingmentioning

confidence: 99%

“…), and alkaline phosphatase (ALP). [11][12][13] Metalloproteases exist in all living organisms, and during eukaryotic evolution the number of metalloproteases expanded, so they became the largest type of protease gene in humans. 14,15 Metalloproteases are inhibited by members of the tissue inhibitor of metalloproteinase (TIMP) family (TIMP1, 2, 3, 4).…”

Section: Introductionmentioning

confidence: 99%

Zingerone Attenuates Pi-induced Vascular Calcification via AMPK-mediated TIMP4 Expression

Lim

Min

Jang

2021

J Lipid Atheroscler

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Objective Vascular calcification requires the differentiation of vascular smooth muscle cells (VSMCs) into osteoblast-like cells. This phenomenon can be enhanced by inflammation and oxidative stress. Zingerone is one of the active ingredients present in the ginger plant that has anti-inflammatory and antioxidant effects. Other functions include anti-obesity, anti-nausea effects. However, the functions of zingerone on vascular calcification has not yet been elucidated. This study investigated the effect of zingerone on vascular calcification and its molecular mechanism. Methods Reverse transcription-polymerase chain reaction (PCR), real-time PCR and Western blot analysis was used to measure expression levels of osteogenic marker genes and to investigate whether calcification was regulated by the expression of AMP-activated protein kinase (AMPK) and tissue inhibitor of metalloproteinase 4 (TIMP4). Alizarin red S staining was used to measure calcium deposition. Studies were carried out in VSMCs. Results Zingerone induced the expression of 2 markers of VSMCs differentiation (α-smooth muscle actin (α-SMA) and smooth muscle 22α (SM22α)) and decreased the expression of core-binding factor α-1 (CBFA1). Additionally, zingerone decreased inorganic phosphate (Pi)-induced expression of distal-less homeobox 5 and CBFA1. AMPK phosphorylation and TIMP4 expression were increased by zingerone. Importantly, zingerone protected VSMCs from calcification, and this protective effect was confirmed by increased TIMP4 via overexpression of AMPK, and inhibition of TIMP4 by Compound C. Zingerone upregulated AMPK/TIMP4 expression and recovered Pi-induced inhibition of TIMP4. Conclusions Taken together, our results show that zingerone inhibits Pi-induced vascular calcification by regulating the AMPK/TIMP4 signaling cascade in VSMCs. These results suggest that the natural product zingerone could be useful for treating vascular and metabolic diseases.

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“…It is important that this process proceeds as a fully functioning system so that increases in osteogenesis by PEMF are not just the result of correcting a culture model but represent stimulation of a process that is similar to bone development/repair. To this end, the attachment-independent 3D culture environment, stable ascorbate protocol [31], mediating effects of estradiol (S9 Fig) [27,28,38], and the robust de novo deposition of prerequisite collagen matrix provide the basic environment for vigorous differentiation of osteoblasts and osteocytes and attendant mineralization. We have focused on mineralization as a late outcome measure of osteogenesis because, in a naïve environment, it requires strong cellular differentiation and activity and thus integrates the success of these steps.…”

Section: Ring Culturementioning

confidence: 99%

Pulsed electromagnetic field (PEMF) transiently stimulates the rate of mineralization in a 3-dimensional ring culture model of osteogenesis

et al. 2021

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Pulsed Electromagnetic Field (PEMF) has shown efficacy in bone repair and yet the optimum characteristics of this modality and its molecular mechanism remain unclear. To determine the effects of timing of PEMF treatment, we present a novel three-dimensional culture model of osteogenesis that demonstrates strong de novo generation of collagen and mineral matrix and exhibits stimulation by PEMF in multiple stages over 62 days of culture. Mouse postnatal day 2 calvarial pre-osteoblasts were cast within and around Teflon rings by polymerization of fibrinogen and cultured suspended without contact with tissue culture plastic. Ring constructs were exposed to PEMF for 4h/day for the entire culture (Daily), or just during Day1-Day10, Day11-Day 27, or Day28-Day63 and cultured without PEMF for the preceding or remaining days, and compared to no-PEMF controls. PEMF was conducted as HF Physio, 40.85 kHz frequency with a 67 ms burst period and an amplitude of 1.19 mT. Osteogenesis was kinetically monitored by repeated fluorescence measurements of continuously present Alizarin Red S (ARS) and periodically confirmed by micro-CT. PEMF treatment induced early-onset and statistically significant transient stimulation (~4-fold) of the mineralization rate when PEMF was applied Daily, or during D1-D10 and D11-D27. Stimulation was apparent but not significant between D28-D63 by ARS but was significant at D63 by micro-CT. PEMF also shifted the micro-CT density profiles to higher densities in each PEMF treatment group. Ring culture generated tissue with a mineral:matrix ratio of 2.0 by thermogravimetric analysis (80% of the calvaria control), and the deposited crystal structure was 50% hydroxyapatite by X-ray diffraction (63% of the calvaria and femur controls), independent of PEMF. These results were consistent with backscatter, secondary electron, and elemental analysis by scanning electron microscopy. Thus, in a defined, strong osteogenic environment, PEMF applied at different times was capable of further stimulation of osteogenesis with the potential to enhance bone repair.

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Estradiol-induced RORα expression positively regulates osteoblast differentiation

Cited by 12 publications

References 27 publications

ROR: Nuclear Receptor for Melatonin or Not?

ROR: Nuclear Receptor for Melatonin or Not?

Zingerone Attenuates Pi-induced Vascular Calcification via AMPK-mediated TIMP4 Expression

Pulsed electromagnetic field (PEMF) transiently stimulates the rate of mineralization in a 3-dimensional ring culture model of osteogenesis

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