Differences in responses to X-ray exposure between osteoclast and osteoblast cells

Abstract Radiation-induced bone loss is a potential health concern for cancer patients undergoing radiotherapy. Enhanced bone resorption by osteoclasts and decreased bone formation by osteoblasts were thought to be the main reasons. In this study, we showed that both pre-differentiating and differentiating osteoclasts were relatively sensitive to X-rays compared with osteoblasts. X-rays decreased cell viability to a greater degree in RAW264.7 cells and in differentiating cells than than in osteoblastic MC3T3-E1 cells. X-rays at up to 8 Gy had little effects on osteoblast mineralization. In contrast, X-rays at 1 Gy induced enhanced osteoclastogenesis by enhanced cell fusion, but had no effects on bone resorption. A higher dose of X-rays at 8 Gy, however, had an inhibitory effect on bone resorption. In addition, actin ring formation was disrupted by 8 Gy of X-rays and reorganized into clusters. An increased activity of Caspase 3 was found after X-ray exposure. Actin disorganization and increased apoptosis may be the potential effects of X-rays at high doses, by inhibiting osteoclast differentiation. Taken together, our data indicate high radiosensitivity of osteoclasts. X-ray irradiation at relatively low doses can activate osteoclastogenesis, but not osteogenic differentiation. The radiosensitive osteoclasts are the potentially responsive cells for X-ray-induced bone loss.

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The effects of x-ray radiation on the eye development of zebrafish

Human & Experimental Toxicology ◽

10.1177/0960327114522278 ◽

2014 ◽

Vol 33 (10) ◽

pp. 1040-1050 ◽

Cited By ~ 19

Author(s):

R Zhou ◽

J Si ◽

H Zhang ◽

Z Wang ◽

J Li ◽

...

Keyword(s):

Eye Development ◽

Model Organism ◽

Control Group ◽

X Rays ◽

Heterogeneous Distribution ◽

X Ray ◽

Radiation Induced ◽

High Doses ◽

Lens Formation ◽

Nuclear Cell

The toxic effects of x-ray radiation on eye development was measured using zebrafish as a model organism. Zebrafish embryos at 8 h post-fertilization (hpf) were irradiated using X-rays at doses of 1, 2, 4, and 8 Gy. At 24 and 48 hpf, x-ray radiation induced a significant increase in reactive oxygen species (ROS) content and cell apoptotic signals. Both of these increases were dose dependent and there were significant positive relationships between them at 24 hpf. At 48 and 72 hpf, the increase of ROS concentration can be eliminated by increasing activities of superoxide dismutase and catalase. Although the ROS generated by x-ray radiation caused a significant increase in cell apoptosis at 24 and 48 hpf, the cellular layers of the retina and lens formation in the irradiated groups were not significantly disrupted at 144 hpf compared with the control group, with the exception of a heterogeneous distribution of the cells in inner nuclear cell layer and a significant decrease in the diameters of whole eyes after 8 Gy irradiation. X-Ray radiation at later stages of gastrulation may not cause distinct optic complications; however, there is still a risk of microophthalmia at high doses of irradiation.

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Is Micro X-ray Computer Tomography a Suitable Non-Destructive Method for the Characterisation of Dental Materials?

Polymers ◽

10.3390/polym13081271 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1271

Author(s):

Andreas Koenig ◽

Leonie Schmohl ◽

Johannes Scheffler ◽

Florian Fuchs ◽

Michaela Schulz-Siegmund ◽

...

Keyword(s):

Flexural Strength ◽

Computer Tomography ◽

Mechanical Performance ◽

Dental Materials ◽

Three Dimensional ◽

X Rays ◽

Scanning Calorimetry ◽

X Ray ◽

Multiple Measurements ◽

High Doses

The aim of the study was to investigate the effect of X-rays used in micro X-ray computer tomography (µXCT) on the mechanical performance and microstructure of a variety of dental materials. Standardised bending beams (2 × 2 × 25 mm3) were forwarded to irradiation with an industrial tomograph. Using three-dimensional datasets, the porosity of the materials was quantified and flexural strength was investigated prior to and after irradiation. The thermal properties of irradiated and unirradiated materials were analysed and compared by means of differential scanning calorimetry (DSC). Single µXCT measurements led to a significant decrease in flexural strength of polycarbonate with acrylnitril-butadien-styrol (PC-ABS). No significant influence in flexural strength was identified for resin-based composites (RBCs), poly(methyl methacrylate) (PMMA), and zinc phosphate cement (HAR) after a single irradiation by measurement. However, DSC results suggest that changes in the microstructure of PMMA are possible with increasing radiation doses (multiple measurements, longer measurements, higher output power from the X-ray tube). In summary, it must be assumed that X-ray radiation during µXCT measurement at high doses can lead to changes in the structure and properties of certain polymers.

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Decitabine Inhibits Bone Resorption in Periodontitis by Upregulating Anti-Inflammatory Cytokines and Suppressing Osteoclastogenesis

Biomedicines ◽

10.3390/biomedicines9020199 ◽

2021 ◽

Vol 9 (2) ◽

pp. 199

Author(s):

Urara Tanaka ◽

Shunichi Kajioka ◽

Livia S. Finoti ◽

Daniela B. Palioto ◽

Denis F. Kinane ◽

...

Keyword(s):

Dna Methylation ◽

Bone Resorption ◽

Bone Loss ◽

Inflammatory Cytokines ◽

Osteoclast Differentiation ◽

Tartrate Resistant Acid Phosphatase ◽

Dependent Manner ◽

Bone Homeostasis ◽

Osteoblastic Cell Line ◽

Anti Inflammatory

DNA methylation controls several inflammatory genes affecting bone homeostasis. Hitherto, inhibition of DNA methylation in vivo in the context of periodontitis and osteoclastogenesis has not been attempted. Ligature-induced periodontitis in C57BL/6J mice was induced by placing ligature for five days with Decitabine (5-aza-2′-deoxycytidine) (1 mg/kg/day) or vehicle treatment. We evaluated bone resorption, osteoclast differentiation by tartrate-resistant acid phosphatase (TRAP) and mRNA expression of anti-inflammatory molecules using cluster differentiation 14 positive (CD14+) monocytes from human peripheral blood. Our data showed that decitabine inhibited bone loss and osteoclast differentiation experimental periodontitis, and suppressed osteoclast CD14+ human monocytes; and conversely, that it increased bone mineralization in osteoblastic cell line MC3T3-E1 in a concentration-dependent manner. In addition to increasing IL10 (interleukin-10), TGFB (transforming growth factor beta-1) in CD14+ monocytes, decitabine upregulated KLF2 (Krüppel-like factor-2) expression. Overexpression of KLF2 protein enhanced the transcription of IL10 and TGFB. On the contrary, site-directed mutagenesis of KLF2 binding site in IL10 and TFGB abrogated luciferase activity in HEK293T cells. Decitabine reduces bone loss in a mouse model of periodontitis by inhibiting osteoclastogenesis through the upregulation of anti-inflammatory cytokines via KLF2 dependent mechanisms. DNA methyltransferase inhibitors merit further investigation as a possible novel therapy for periodontitis.

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Inhibitory Effect of (2R)-4-(4-hydroxyphenyl)-2-butanol 2-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside on RANKL-Induced Osteoclast Differentiation and ROS Generation in Macrophages

International Journal of Molecular Sciences ◽

10.3390/ijms22010222 ◽

2020 ◽

Vol 22 (1) ◽

pp. 222

Author(s):

Eun-Nam Kim ◽

Ga-Ram Kim ◽

Jae Sik Yu ◽

Ki Hyun Kim ◽

Gil-Saeng Jeong

Keyword(s):

Bone Loss ◽

Bone Formation ◽

Bone Disease ◽

Osteoclast Differentiation ◽

Inhibitory Effect ◽

Bone Diseases ◽

Ros Generation ◽

Bone Homeostasis ◽

Disease Treatment ◽

And Migration

In bone homeostasis, bone loss due to excessive osteoclasts and inflammation or osteolysis in the bone formation process cause bone diseases such as osteoporosis. Suppressing the accompanying oxidative stress such as ROS in this process is an important treatment strategy for bone disease. Therefore, in this study, the effect of (2R)-4-(4-hydroxyphenyl)-2-butanol 2-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside (BAG), an arylbutanoid glycoside isolated from Betula platyphylla var. japonica was investigated in RANKL-induced RAW264.7 cells and LPS-stimulated MC3E3-T1 cells. BAG inhibited the activity of TRAP, an important marker of osteoclast differentiation and F-actin ring formation, which has osteospecific structure. In addition, the protein and gene levels were suppressed of integrin β3 and CCL4, which play an important role in the osteoclast-induced bone resorption and migration of osteoclasts, and inhibited the production of ROS and restored the expression of antioxidant enzymes such as SOD and CAT lost by RANKL. The inhibitory effect of BAG on osteoclast differentiation and ROS production appears to be due to the inhibition of MAPKs phosphorylation and NF-κβ translocation, which play a major role in osteoclast differentiation. In addition, BAG inhibited ROS generated by LPS and effectively restores the mineralization of lost osteoblasts, thereby showing the effect of bone formation in the inflammatory situation accompanying bone loss by excessive osteoclasts, suggesting its potential as a new natural product-derived bone disease treatment.

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Capsaicin, a TRPV1 Ligand, Suppresses Bone Resorption by Inhibiting the Prostaglandin E Production of Osteoblasts, and Attenuates the Inflammatory Bone Loss Induced by Lipopolysaccharide

ISRN Pharmacology ◽

10.5402/2012/439860 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 11

Author(s):

Megumi Kobayashi ◽

Kenta Watanabe ◽

Satoshi Yokoyama ◽

Chiho Matsumoto ◽

Michiko Hirata ◽

...

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Transient Receptor Potential ◽

Interleukin 1 ◽

Osteoclast Differentiation ◽

Bone Diseases ◽

Prostaglandin E ◽

Transient Receptor Potential Vanilloid ◽

Cox 2

Capsaicin, a transient receptor potential vanilloid type 1 (TRPV1) ligand, regulates nerve-related pain-sensitive signals, inflammation, and cancer growth. Capsaicin suppresses interleukin-1-induced osteoclast differentiation, but its roles in bone tissues and bone diseases are not known. This study examined the effects of capsaicin on inflammatory bone resorption and prostaglandin E (PGE) production induced by lipopolysaccharide (LPS) in vitro and on bone mass in LPS-treated mice in vivo. Capsaicin suppressed osteoclast formation, bone resorption, and PGE production induced by LPS in vitro. Capsaicin suppressed the expression of cyclooxygenase-2 (COX-2) and membrane-bound PGE synthase-1 (mPGES-1) mRNAs and PGE production induced by LPS in osteoblasts. Capsaicin may suppress PGE production by inhibiting the expression of COX-2 and mPGES-1 in osteoblasts and LPS-induced bone resorption by TRPV1 signals because osteoblasts express TRPV1. LPS treatment markedly induced bone loss in the femur in mice, and capsaicin significantly restored the inflammatory bone loss induced by LPS in mice. TRPV1 ligands like capsaicin may therefore be potentially useful as clinical drugs targeting bone diseases associated with inflammatory bone resorption.

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The inhibitory effect of vitamin K on RANKL-induced osteoclast differentiation and bone resorption

Food & Function ◽

10.1039/c5fo00544b ◽

2015 ◽

Vol 6 (10) ◽

pp. 3351-3358 ◽

Cited By ~ 10

Author(s):

Wei-Jie Wu ◽

Min Seuk Kim ◽

Byung-Yong Ahn

Keyword(s):

Bone Resorption ◽

Vitamin K ◽

Osteoclast Differentiation ◽

Inhibitory Effect

Vitamins K1, MK-4 and MK-7 have anti-osteoporotic properties, while their regulation effects on osteoclastogenesis are somewhat different.

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Effect of Icariin on Osteoclasts and Its Mechanism

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2020.2509 ◽

2020 ◽

Vol 10 (12) ◽

pp. 1807-1812

Author(s):

Xiaoxiao Wu ◽

Xi Fu ◽

Xiabing Qin

Keyword(s):

Transcription Factors ◽

Bone Resorption ◽

Bone Loss ◽

Mapk Pathway ◽

Early Stage ◽

Osteoclast Differentiation ◽

Mapk Signaling ◽

Therapeutic Drug ◽

Actin Ring ◽

B Subunit

Background: The paper aimed to elucidate the molecular mechanism of Icariin regulating RANKLinduced osteoclast-ogenesis and bone resorption, and to investigate whether Icariin could be a potential therapeutic drug for diseases of bone loss related to osteoclast. Material and methods: Osteoclasts were cultured. MTT to determine cell viability. Von Kossa to determine the effect of Icariin on bone resorption. F-actin ring staining to measure the expressions of various proteins, and WB method was used to measure the expression of p-65. Results: MTT showed that Icariin is not toxic to osteoclasts. The bone resorption result showed that RANKL-mediated osteoclast bone resorption was reduced in the early stage, and the higher the intervention concentration, the smaller the bone resorption area. F-actin ring staining indicated that it is possible to reduce the differentiation and bone resorption capacity of osteoclasts by hindering the formation of F-actin ring in the early stage, and in a concentration-dependentmanner. Significantly reduced the expressions of key transcription factors-NFATc1 and c-Fos. It significantly inhibited the phosphorylation and nucleation of NF-κB subunit p65 induced by RANKL, and significantly inhibited the phosphorylation of ERK and p38 proteins in the MAPK pathway activated by RANKL. Conclusion: Icariin can effectively inhibit osteoclast differentiation, F-actin ring formation, and bone resorption. By inhibiting the key transcription factors NFATc1 and c-Fos to down-regulate related expressions, thereby impeding osteoclast differentiation, Icariin may regulate key transcription factors NFATc1 and c-Fos through NF-κB and MAPK signaling pathways. Studies have suggested that Icariin could be a potential treatment for diseases of bone loss related to osteoclasts.

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IX. Nucleinsäuregehalt und Nucleinsäuresynthese nach Röntgenbestrahlung

Zeitschrift für Naturforschung B ◽

10.1515/znb-1966-1011 ◽

1966 ◽

Vol 21 (10) ◽

pp. 960-966 ◽

Cited By ~ 6

Author(s):

Yasuhiko Takamori ◽

Ernst-Randolf Lochmann ◽

Wolfgang Laskowski

Keyword(s):

Ribosomal Rna ◽

Rna Synthesis ◽

Small Difference ◽

Dry Weight ◽

Nucleic Acid Content ◽

X Rays ◽

X Ray ◽

Dna And Rna ◽

High Doses ◽

Different Doses

The amount of DNA and RNA per dry weight as well as the rate of RNA synthesis was determined in a series of almost isogenic and homozygous Saccharomyces strains of different ploidy which had irradiated with different doses of X-rays.It was found that the RNA content per dry weight showed only a small decrease after irradiation even with high doses. The decrease in the DNA content after irradiation is larger, and it is already maximal at the smallest X-ray dose tested (75 krad) . No further decrease could be observed even after application of 225 krad.The RNA synthesis is much more radioresistant in all strains tested (haploid-hexaploid) than the colony forming ability. X-ray doses which reduce the colony forming ability of the cells to less than 1% lead to a reduction of the RNA synthesis of only about 50 per cent. The inactivation of RNA synthesis increases with increasing irradiation doses and increasing incubation time after irradiation.There was only a small difference in the radiosensitivity of the synthesis of soluble or ribosomal RNA.Genetic effects on the radiation inactivation of the colony forming ability, previously described as “aα-effect” and “AS-effect”, show no influence on the radiosensitivity of cellular nucleic acid content and synthesis.

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Piceatannol attenuates RANKL-induced osteoclast differentiation and bone resorption by suppressing MAPK, NF-κB and AKT signalling pathways and promotes Caspase3-mediated apoptosis of mature osteoclasts

Royal Society Open Science ◽

10.1098/rsos.190360 ◽

2019 ◽

Vol 6 (6) ◽

pp. 190360 ◽

Cited By ~ 5

Author(s):

Liuliu Yan ◽

Lulu Lu ◽

Fangbin Hu ◽

Dattatrya Shetti ◽

Kun Wei

Keyword(s):

Bone Resorption ◽

Osteoclast Differentiation ◽

Giant Cells ◽

Inhibitory Effect ◽

Osteoclast Formation ◽

Bone Diseases ◽

Signalling Pathways ◽

Dependent Manner ◽

Underlying Mechanisms ◽

And Function

Osteoclasts are multinuclear giant cells that have unique ability to degrade bone. The search for new medicines that modulate the formation and function of osteoclasts is a potential approach for treating osteoclast-related bone diseases. Piceatannol (PIC) is a natural organic polyphenolic stilbene compound found in diverse plants with a strong antioxidant and anti-inflammatory effect. However, the effect of PIC on bone health has not been scrutinized systematically. In this study, we used RAW264.7, an osteoclast lineage of cells of murine macrophages, to investigate the effects and the underlying mechanisms of PIC on osteoclasts. Here, we demonstrated that PIC treatment ranging from 0 to 40 µM strongly inhibited osteoclast formation and bone resorption in a dose-dependent manner. Furthermore, the inhibitory effect of PIC was accompanied by the decrease of osteoclast-specific genes. At the molecular level, PIC suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK1/2), NF-κB p65, IκBα and AKT. Besides, PIC promoted the apoptosis of mature osteoclasts by inducing caspase-3 expression. In conclusion, our results suggested that PIC inhibited RANKL-induced osteoclastogenesis and bone resorption by suppressing MAPK, NF-κB and AKT signalling pathways and promoted caspase3-mediated apoptosis of mature osteoclasts, which might contribute to the treatment of bone diseases characterized by excessive bone resorption.

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