Radioprotection of Osteoblasts by a Fractionated Dose Regimen and Amifostine

Wong, Alex K.; Mei, Lily; Soares, Marc A.; Schönmeyr, Björn; Mehrara, Babak J.

doi:10.1097/prs.0b013e318191c5a0

Cited by 4 publications

(16 citation statements)

References 28 publications

(31 reference statements)

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“…Therefore, it is reasonable to put more emphasis on osteoblasts when studying irradiation effects on osseointegration. In several in vitro studies, it was believed that irradiation inhibited cell proliferation dose dependently, whereas the influence of irradiation on cell differentiation remained controversial 4–9. Some authors reported a promotion of cellular differentiation of osteoblast‐like cells after exposure to ionizing radiation 4, 6, 10.…”

Section: Introductionmentioning

confidence: 99%

Effects of irradiation on osteoblast‐like cells on different titanium surfacesin vitro

Feng

et al. 2012

J Biomed Mater Res

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The aim of this study was to investigate the effects of irradiation on adhesion ability, proliferation, and differentiation of MC3T3-E1 cells on microarc oxidation (MAO) titanium surfaces and polished titanium (PT) surfaces. MC3T3-E1 cells were exposed to a single dose at 2, 4, 6, 8, or 10 Gy using a (60) Co source, with tissue culture polystyrene plates chosen as controls. On all surfaces, irradiation resulted in a dose-dependent decrease in cellular proliferation. At 4 Gy dose, the cell proliferation of cells decreased by 17.8% on MAO and 18.6% on PT surfaces, respectively, compared with nonirradiated controls. Cells exposed to 8 Gy dose showed significant inhibition in collagen secretion and osteogenesis-related genes expression (OSX, COL-Iα1, and OCN). In contrast, irradiation increased cell adhesion to three surfaces dose dependently. It was also demonstrated that cells on MAO surface showed higher adhesion and collagen secretion than on PT surface at different radiation doses. This study revealed the effects of irradiation on osteoblasts in vitro on two titanium surfaces. MAO surface could be used in dental implants in irradiated bone due to enhanced adhesion ability and collagen secretion in osteoblasts.

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Section: Introductionmentioning

confidence: 99%

Effects of irradiation on osteoblast‐like cells on different titanium surfacesin vitro

Feng

et al. 2012

J Biomed Mater Res

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“…1,13,14 Prolonged exposure to spaceflight radiation harms astronauts' health by increasing the number and activity of osteoclasts, 1,14,15 which decreases the bone mineral density (BMD). [21][22][23][24] In an in vitro study, Wong et al 25 demonstrated that AMI showed a protective effect on normal osteoblastic differentiation in irradiated bone, and AMI could increase the activity of ALP in cells compared to that of radiation-only cells. 14,16 Recently, Buchman and Margulies demonstrated that amifostine (AMI) could elevate BMD, short fracture healing time, and increase the formation of bone mass in irradiated bones.…”

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confidence: 99%

“…It also may cause a high risk of fracture and osteoporosis. 22,25 In an in vivo study, the regenerated BMD was significantly diminished by radiation therapy in a distraction osteogenesis model of the murine jaw. 17,18 In vivo, AMI could transform into a clinically active metabolite (WR-1065) by rapidly dephosphorylating by alkaline phosphatase (ALP).…”

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confidence: 99%

“…14,16 Recently, Buchman and Margulies demonstrated that amifostine (AMI) could elevate BMD, short fracture healing time, and increase the formation of bone mass in irradiated bones. 22,25 In vivo studies [22][23][24][25] have proved that bone quality and bone quantity could be increased by AMI in irradiated models. After activation, cells could be protected from radiationinduced DNA damage, for AMI cloud prevent DNA double-strand damage and eliminate ROS induced by radiotherapy.…”

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confidence: 99%

“…17,18 In vivo, AMI could transform into a clinically active metabolite (WR-1065) by rapidly dephosphorylating by alkaline phosphatase (ALP). [22][23][24][25] However, whether AMI could affect the differentiation of RAW264.7 cells into osteoclasts and how it affects RAW264.7 under radiotherapy are still unclear. At the same time, a large number of hydrogen ions are produced during the activation of AMI, which helps to repair DNA damage caused by radiation.…”

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confidence: 99%

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Amifostine inhibited the differentiation of RAW264.7 cells into osteoclasts by reducing the production of ROS under 2 Gy radiation

Zhang

Huang

Tang

et al. 2019

J of Cellular Biochemistry

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Patients with malignant tumors receive radiotherapy, and radiation could harm the skeletal system, leading to radiation‐induced osteoporosis. A major cause of this phenomenon is the activation of osteoclasts by radiotherapy. In this study, we studied whether amifostine (AMI) could affect the differentiation of osteoclast precursor cells (RAW264.7 cells) into osteoclasts under 2 gray (Gy) radiation. Four groups were used in the experiment: (a) 0 Gy (no radiation); (b) 0 Gy + AMI; (c) 2 Gy radiation; and (d) 2 Gy radiation + AMI. After radiation, a proliferation assay, a reactive oxygen species (ROS) assay, a comet assay, Trap staining, reverse transcription polymerase chain reaction, and an animal study to test the effect of AMI on osteoclast precursor cells under 2 Gy radiation were conducted. Cell proliferation was significantly inhibited by AMI (P < .05). In addition, 2 Gy radiation led to longer “comet tails”, high level of ROS, and more Trap‐positive cells in vivo and in vitro (P < .05). Radiation improved the expression of CSTK, NFAT, and Rankl/OPG gene (P < .05), as well as Trap‐5b levels in the serum, and decreased bone mineral density. AMI inhibited the differentiation of RAW264.7 cells, shortened the tail moment length of comets, and decreased the level of ROS induced by radiation. The expression of NFAT, CTSK, and Rankl/OPG was decreased by AMI at the detection time point in radiation groups (P < .05). AMI inhibits the maturation and differentiation of osteoclasts under radiation conditions by reducing DNA damage and ROS induced by radiation, thereby reducing the adverse effects of radiation in the skeletal system, indicating that AMI might be used to treat osteoradionecrosis.

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Amifostine Treatment Mitigates the Damaging Effects of Radiation on Distraction Osteogenesis in the Murine Mandible

Monson

Nelson

Donneys³

et al. 2016

Annals of Plastic Surgery

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According to the American Society of Clinical Oncology, in 2012, more than 53,000 new cases of head and neck cancers (HNCs) were reported in the United States alone and nearly 12,000 deaths occurred relating to HNC. Although radiotherapy (XRT) has increased survival, the adverse effects can be unrelenting and their management is rarely remedial. Current treatment dictates surgical mandibular reconstruction using free tissue transfer. These complex operations entail extended hospitalizations and attendant complications often lead to delays in initiation of adjuvant therapy, jeopardizing prognosis as well as quality of life. The creation of new bone by distraction osteogenesis (DO) generates a replacement of deficient tissue from local substrate and could have immense potential therapeutic ramifications. Radiotherapy drastically impairs bone healing, precluding its use as a reconstructive method for HNC. We posit that the deleterious effects of XRT on bone formation could be pharmacologically mitigated. To test this hypothesis, we used a rodent model of DO and treated with amifostine, a radioprotectant, to assuage the XRT-induced injury on new bone formation. Amifostine had a profound salutary effect on bone regeneration, allowing the successful implementation of DO as a reconstructive technique. The optimization of bone regeneration in the irradiated mandible has immense potential for translation from the bench to the bedside, providing improved therapeutic options for patients subjected to XRT.

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Radioprotection of Osteoblasts by a Fractionated Dose Regimen and Amifostine

Cited by 4 publications

References 28 publications

Effects of irradiation on osteoblast‐like cells on different titanium surfacesin vitro

Effects of irradiation on osteoblast‐like cells on different titanium surfacesin vitro

Amifostine inhibited the differentiation of RAW264.7 cells into osteoclasts by reducing the production of ROS under 2 Gy radiation

Amifostine Treatment Mitigates the Damaging Effects of Radiation on Distraction Osteogenesis in the Murine Mandible

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