Ionizing radiation sensitizes bone cells to apoptosis

Szymczyk, K. H.; Shapiro, Irving M.; Adams, Christopher S.

doi:10.1016/j.bone.2003.09.003

Cited by 110 publications

(70 citation statements)

References 29 publications

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“…The results are consistent with previous reports on ionizing radiation effect on cells. 19,23,41 Thus, the radiation induced a growth inhibition that was largely due to cell cycle inhibition, senescence, and/or cell death.…”

Section: Discussionmentioning

confidence: 99%

Live-cell imaging to detect phosphatidylserine externalization in brain endothelial cells exposed to ionizing radiation: implications for the treatment of brain arteriovenous malformations

Zhao

Johnson

Chen

et al. 2016

JNS

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Brain arteriovenous malformations (AVMs) are congenital abnormalities that consist of direct connections between arteries and veins, allowing highpressure arterial blood to flow into fragile cerebral veins, resulting in a high risk of hemorrhagic stroke. 16,37 The aim of AVM treatment is to prevent hemorrhage. 29 Treatment is effective only with complete AVM removal or obliteration. 14 Current treatments-namely surgery, endovascular occlusion, or stereotactic radiosurgery-are all associated with significant limitations.1,42 The surgical risk is generally unacceptable for lesions that are large, located in critical brain structures, or involve deep perforating arterabbreviatioNs AVM = arteriovenous malformation; FWD = forward; PI = propidium iodide; PS = phosphatidylserine; pSIVA = polarity-sensitive indicator of viability and apoptosis; SRS = stereotactic radiosurgery. obJective Stereotactic radiosurgery (SRS) is an established intervention for brain arteriovenous malformations (AVMs). The processes of AVM vessel occlusion after SRS are poorly understood. To improve SRS efficacy, it is important to understand the cellular response of blood vessels to radiation. The molecular changes on the surface of AVM endothelial cells after irradiation may also be used for vascular targeting. This study investigates radiation-induced externalization of phosphatidylserine (PS) on endothelial cells using live-cell imaging. methods An immortalized cell line generated from mouse brain endothelium, bEnd.3 cells, was cultured and irradiated at different radiation doses using a linear accelerator. PS externalization in the cells was subsequently visualized using polarity-sensitive indicator of viability and apoptosis (pSIVA)-IANBD, a polarity-sensitive probe. Live-cell imaging was used to monitor PS externalization in real time. The effects of radiation on the cell cycle of bEnd.3 cells were also examined by flow cytometry. results Ionizing radiation effects are dose dependent. Reduction in the cell proliferation rate was observed after exposure to 5 Gy radiation, whereas higher radiation doses (15 Gy and 25 Gy) totally inhibited proliferation. In comparison with cells treated with sham radiation, the irradiated cells showed distinct pseudopodial elongation with little or no spreading of the cell body. The percentages of pSIVA-positive cells were significantly higher (p = 0.04) 24 hours after treatment in the cultures that received 25- and 15-Gy doses of radiation. This effect was sustained until the end of the experiment (3 days). Radiation at 5 Gy did not induce significant PS externalization compared with the sham-radiation controls at any time points (p > 0.15). Flow cytometric analysis data indicate that irradiation induced growth arrest of bEnd.3 cells, with cells accumulating in the G2 phase of the cell cycle. coNclusioNs Ionizing radiation causes remarkable cellular changes in endothelial cells. Significant PS externalization is induced by radiation at doses of 15 Gy or higher, concomitant with a block in the cell cycle. Ra...

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Section: Discussionmentioning

confidence: 99%

Live-cell imaging to detect phosphatidylserine externalization in brain endothelial cells exposed to ionizing radiation: implications for the treatment of brain arteriovenous malformations

Zhao

Johnson

Chen

et al. 2016

JNS

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“…It is concidered that missing of bone mass occur because of the bone osteoblastic formation and bone vasculature damages (14)(15)(16). Ionizing radiation inhibits osteoblast proliferation, increases sensitivity to agents that induce apoptosis, and reduces collagen production (17)(18)(19). After exposure to radiation, quantity of osteoblast in first month decreases progressivly (20,21).…”

Section: Discussionmentioning

confidence: 99%

The Effects of Radiation on Bone Mineral Density of Radiology Workers Depending on The Device They Use

Kunt

Dayıoğlu

2011

ELECTRON J GEN MED

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“…To evaluate cell death, osteoblast-like cells were plated on experimental (RGDS) and control (RGES) substrates in 12-or 24-well plates at a density of 50,000/well or 25,000/well, respectively. After 3 days in culture in complete media, the osteoblasts were incubated overnight with sublethal doses of staurosporine (0.1 and 0.5 M) (32,33), the Ca 2ϩ (2.4 and 2.9 mM) and P i (3 mM) ion pair (27), sodium nitroprusside (0.5 and 0.1 mM) (34), or RGDS (1 mM and 5 mM) (13) or were serum-starved (35). The ion pair, sodium nitroprusside, and staurosporine all induce cell death through the intrinsic pathway; RGDS and serum starvation probably kill osteoblasts by a mitochondria-independent pathway.…”

Section: Cell Culturementioning

confidence: 99%

Apoptosis and Survival of Osteoblast-like Cells Are Regulated by Surface Attachment

Grigoriou

Shapiro²,

Cavalcanti‐Adam

et al. 2005

Journal of Biological Chemistry

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We tested the hypothesis that RGDS peptides regulate osteoblast survival in culture. Osteoblast-like MC3T3-E1 cells were allowed to attach to RGDS peptides that had been tethered to a silicone surface utilizing a previously described grafting technique. The RGDS-modified surface caused up-regulation of ␣ v ␤ 3 integrin. We noted that there was an increase in expression of activated focal adhesion kinase and activated Akt. There was no change in the expression level of the anti-apoptotic protein Bcl-2, the pro-apoptotic protein Bad, or the inactivated form of Bad, pBad. Attachment to the RGDStreated membrane completely abolished apoptosis induced by staurosporine, the Ca 2؉ ⅐P i ion pair, and sodium nitroprusside. However, the surface modification did not interfere with apoptosis mediated by the free RGDS peptide or serum-free medium. When the activity of the phosphatidylinositol 3-kinase pathway was inhibited, RGDS-dependent resistance to apoptosis was eliminated. These results indicated that the binding of cells to RGDS abrogated apoptosis via the mitochondrial pathway and that the suppression of apoptosis was dependent on the activity of phosphatidylinositol 3-kinase.Osteoblast survival requires attachment to specific extracellular matrix proteins, a phenomenon termed anchorage dependence (1). The survival signal is mediated by transmembrane integrin receptors that provide a mechanical link between the cell and the hydrophilic peptide sequence Arg-GlyAsp (RGD) on extracellular macromolecules (2, 3). This amino acid motif enhances initial osteoblast attachment and spreading (4, 5). In addition to influencing downstream maturation events (6), RGD signaling (7) induces mineralization of the extracellular matrix (8, 9). Likewise, exposure of osteoblasts to immobilized RGD peptides increases osteoblast maturation (9 -12); at millimolar concentrations, free RGD-containing peptides induce skeletal cell death (13).The interaction between the RGD motif and integrin receptors causes phosphorylation of the non-receptor protein-tyrosine kinase and activation of focal adhesion kinase (FAK) 1 (14, 15). Once phosphorylated, FAK provides binding sites for Src homology-2 domains of the survival signaling pathway molecules Grb2-Sos and phosphatidylinositol 3-kinase (PI3K) (16,17). Of the downstream targets of PI3K, Akt plays a critical role in the regulation of the balance between apoptosis and survival. Once the Akt pathway is activated, there is stimulation of a number of downstream events that include: phosphorylation and inactivation of caspase-9, resulting in inhibition of apoptosis and enhancement of cell survival (18, 19); maintenance of the mitochondrial membrane potential and suppression of mitochondrion-initiated apoptosis (20); and phosphorylation of Bad and prevention of mitochondrial dysfunction (18,21). In addition, activated Akt phosphorylates a number of cell survival-related transcription factors, including Forkhead 1 (22), 24), and Creb (25).Despite overwhelming evidence that relates integrin-mediated adhesion...

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Ionizing radiation sensitizes bone cells to apoptosis

Cited by 110 publications

References 29 publications

Live-cell imaging to detect phosphatidylserine externalization in brain endothelial cells exposed to ionizing radiation: implications for the treatment of brain arteriovenous malformations

Live-cell imaging to detect phosphatidylserine externalization in brain endothelial cells exposed to ionizing radiation: implications for the treatment of brain arteriovenous malformations

The Effects of Radiation on Bone Mineral Density of Radiology Workers Depending on The Device They Use

Apoptosis and Survival of Osteoblast-like Cells Are Regulated by Surface Attachment

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