&lt;p&gt;Cerium Oxide Nanoparticles Regulate Osteoclast Differentiation Bidirectionally by Modulating the Cellular Production of Reactive Oxygen Species&lt;/p&gt;

Yuan, Kai; Mei, Jingtian; Shao, Dandan; Zhou, Feng; Qiao, Han; Liang, Yuhua; Li, Kai; Tang, Tingting

doi:10.2147/ijn.s257741

Cited by 40 publications

(40 citation statements)

References 57 publications

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“…There has been conflicting literature about cerium oxide nanoparticles’ ability to induce radiosensitization, despite being a metal with a high z number, with some studies showing radiosensitizing abilities [ 37 , 50 , 51 , 52 ], including in breast cancer [ 53 ], while others reporting it as a radioprotector [ 54 , 55 , 56 ]. Moreover, reports on the subcellular distribution of unmodified CeO 2 nanoparticles also varied widely based on the type of cells: in neuronal stem cells, they were predominantly localized in membrane-bound structures and, to a lesser extent, were found free in the cytoplasm, with none detected in the nucleus or other structures [ 57 ]; in gastric cancer cells, they were reported to be localized in lysosomes and in no other parts of the cell [ 58 ]; in human keratinocyte cells, they were localized in mitochondria, lysosomes, and endoplasmic reticulum, as well as being abundant in the cytoplasm and the nucleus [ 59 ]; however, in bone marrow-derived macrophages, the CeO 2 nanoparticles entered the nucleus and were found to disrupt the integrity of the cell membrane and organelles [ 60 ]. Moreover, it has been reported that the subcellular location of the nanoceria affected their cytotoxicity profiles, with minimal toxicity observed when localized in the cytoplasm and exhibiting significant cytotoxicity when present in the lysosomal compartment [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Internalized Nanoceria Modify the Radiation-Sensitivity Profile of MDA MB231 Breast Carcinoma Cells

Bibb

Alajlan

Alsuwailem

et al. 2021

Biology

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Owing to its unique redox properties, cerium oxide (nanoceria) nanoparticles have been shown to confer either radiosensitization or radioprotection to human cells. We investigated nanoceria’s ability to modify cellular health and reactive oxygen species (ROS) at various absorbed doses (Gray) of ionizing radiation in MDA-MB231 breast carcinoma cells. We used transmission electron microscopy to visualize the uptake and compartmental localization of nanoceria within cells at various treatment concentrations. The effects on apoptosis and other cellular health parameters were assessed using confocal fluorescence imaging and flow cytometry without and with various absorbed doses of ionizing radiation, along with intracellular ROS levels. Our results showed that nanoceria were taken up into cells mainly by macropinocytosis and segregated into concentration-dependent large aggregates in macropinosomes. Confocal imaging and flow cytometry data showed an overall decrease in apoptotic cell populations in proportion to increasing nanoparticle concentrations. This increase in cellular health was observed with a corresponding reduction in ROS at all tested absorbed doses. Moreover, this effect appeared pronounced at lower doses compared to unirradiated or untreated populations. In conclusion, internalized nanoceria confers radioprotection with a corresponding decrease in ROS in MDA-MB231 cells, and this property confers significant perils and opportunities when utilized in the context of radiotherapy.

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Section: Discussionmentioning

confidence: 99%

Internalized Nanoceria Modify the Radiation-Sensitivity Profile of MDA MB231 Breast Carcinoma Cells

Bibb

Alajlan

Alsuwailem

et al. 2021

Biology

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“…RANKL-induced BMMs activate MAPK and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signals and cause osteoclast differentiation. MAPK signal is induced by the phosphorylation of ERK, JNK, and P38 in RANKL-induced osteoclasts [ 41 ]. In the NF-κB pathway, IκBα inhibits the initiation of the NF-κB signal pathway.…”

Section: Discussionmentioning

confidence: 99%

“…However, IκBα is phosphorylated by RANKL. In other words, the phosphorylation of IκBα leads to osteoclast differentiation [ 40 , 41 , 42 ]. GNPs slightly inhibited RANKL-induced phosphorylation of ERK, JNK, IκBα, and p65, whereas SNP groups further inhibited the phosphorylation ( Figure 6 ).…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of Gold and Silver Nanoparticles on the Differentiation into Osteoclasts In Vitro

Lee

Kim

et al. 2021

Pharmaceutics

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Gold nanoparticles (GNPs) have been widely studied to inhibit differentiation into osteoclasts. However, reports of the inhibitory effects of silver nanoparticles (SNPs) during the process of differentiation into osteoclasts are rare. We compared the inhibitory effect of GNPs and SNPs during the process of differentiation into osteoclasts. Bone marrow-derived cells were differentiated into osteoclasts by the receptor activator of the nuclear factor-kappa-Β ligand (RANKL). The inhibitory effect of GNPs or SNPs during the process of differentiation into osteoclasts was investigated using tartrate-resistant acid phosphatase (TRAP) and actin ring staining. The formation of TRAP positive (+) multinuclear cells (MNCs) with the actin ring structure was most inhibited in the SNP group. In addition, the expression of specific genes related to the differentiation into osteoclasts, such as c-Fos, the nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), TRAP, and Cathepsin K (CTSK) were also inhibited in the SNP groups. As a result, the levels related to differentiation into osteoclasts were consistently lower in the SNP groups than in the GNP groups. Our study suggests that SNPs can be a useful material for inhibiting differentiation into osteoclasts and they can be applied to treatments for osteoporosis patients.

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“…Next, the effects of SOG treatment on osteoclast-mediated bone resorption and F-actin ring formation of osteoclasts were examined. It is acknowledged that the formation of well-de ned F-actin ring was indispensable for osteoclastic function 4 . Figure 2a showed that the number and size of F-actin rings were effectively diminished with the increase of the concentration of SOG.…”

Section: Sog Inhibited Rankl-induced Osteoclast Formationmentioning

confidence: 99%

“…Previous studies suggested that in ammation and oxidative stress could promote osteoclast differentiation, leading to osteolysis 3,4 . Therefore, inhibition of excessive osteoclast formation and bone resorption activity has been regarded as an important therapeutic strategy for bone lysis diseases.…”

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confidence: 99%

Sec-O-glucosylhamaudol Inhibits RANKL-induced Osteoclastogenesis Via Repressing 5-LO and AKT/GSK3β Signaling

Cao

Zhou

Chen

et al. 2021

Preprint

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BackgroundOsteoclast excessive activation was closely related to bone diseases such as osteoporosis and rheumatoid arthritis. Sec-O-glucosylhamaudol (SOG), an active flavonoid compound derived from the root of divaricate Saposhnikovia, was reported to exhibit analgesic, anti-inflammatory and high 5-lipoxygenase (5-LO) inhibitory effects. However, its effect on osteoclastogenesis and bone resorption remained unclear.MethodsOsteoclast formation, bone resorption pit area formation and F-actin ring formation were examined by TRAP staining, modified Vonkonsa staining and immunofluorescence, respectively. RT-Realtime PCR assay and western blot analysis were performed. siRNA transfection was conducted to silence the expression of 5-LO in cells. LPS-induced bone-loss mice model was prepared and the left and right femurs were collected for Micro-CT and histomorphometric analysis, respectively.ResultsSOG markedly attenuated RANKL-induced osteoclastogenesis through decreasing TRAP activity, F-actin ring formation and bone resorption with reduction of mRNA levels of osteoclastogenesis marker genes such as TRAP, CTSK and DC-STAMP. Our results further indicated that SOG markedly reduced the induction of key transcription factors NFATc1 and c-Fos at both mRNA and protein levels during osteoclastogenesis. In addition, SOG treatment did not alter the transient phosphorylation of NF-κB p65 subunit and MAPKs (p38, ERK1/2 and JNK), AKT and GSK3β by RANKL. Interestingly, our results showed that SOG significantly inhibited the phosphorylation of AKT and GSK3β at middle-late stage of osteoclastogenesis, but did not alter calcineurin catalytic subunit PP2B-Aα expression. GSK3β inhibitor SB415286 could partly reverse inhibition of osteoclastogenesis by SOG. 5-LO knockdown at BMMs also markedly reduced RANKL-induced osteoclastogenesis. In consistent with in vitro results，SOG could significantly improve bone destruction in LPS-induced mice model.ConclusionsSOG attenuated formation and function of osteoclast through suppressing AKT-mediated GSK3β inactivation, and 5-LO catalytic activity. Moreover, SOG prevented LPS-induced bone loss in mice through inhibiting osteoclastogenesis. Taken together, this study provided the evidence that SOG may have a potential therapeutic effect on osteoclast-related bone lysis disease.

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<p>Cerium Oxide Nanoparticles Regulate Osteoclast Differentiation Bidirectionally by Modulating the Cellular Production of Reactive Oxygen Species</p>

Cited by 40 publications

References 57 publications

Internalized Nanoceria Modify the Radiation-Sensitivity Profile of MDA MB231 Breast Carcinoma Cells

Internalized Nanoceria Modify the Radiation-Sensitivity Profile of MDA MB231 Breast Carcinoma Cells

Inhibitory Effects of Gold and Silver Nanoparticles on the Differentiation into Osteoclasts In Vitro

Sec-O-glucosylhamaudol Inhibits RANKL-induced Osteoclastogenesis Via Repressing 5-LO and AKT/GSK3β Signaling

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