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Radiation alters osteoclastogenesis by regulating the cytoskeleton and lytic enzymes in RAW 264.7 cells and mouse bone marrow-derived macrophages.
International Journal of Radiation Biology ( IF 2.6 ) Pub Date : 2020-08-03 , DOI: 10.1080/09553002.2020.1798542
Ling Tong 1, 2 , Yuyang Wang 1 , Jianping Wang 1 , Feilong He 1, 2 , Jianglong Zhai 1 , Jiangtao Bai 1 , Guoying Zhu 1
Affiliation  

Abstract

Purpose

The aim of the present study was to investigate the duality of irradiation effect on osteoclastogenesis, particularly on the cytoskeleton and expression of lytic enzymes in osteoclast precursors. Therefore, the present study may serve as a useful reference for the prevention and treatment of radiation-induced bone loss in the clinic.

Materials and methods

Two typical osteoclast precursors, murine RAW 264.7 macrophage cells and mouse bone marrow-derived macrophages (BMMs), were exposed to radiation in the order of 0.25–8 Gy, and the effects on cell viability, TRAP activity and bone resorption were subsequently investigated. Furthermore, changes in the cytoskeleton, cell apoptosis, and expression of lytic enzymes in osteoclasts were examined to elucidate the molecular mechanism of the duality of irradiation on osteoclastogenesis.

Results

Morphological changes and impaired viability were observed in RAW 264.7 cells and BMMs treated with 1–8 Gy irradiation with or without RANKL. However, the cell fusion tendency of osteoclasts was enhanced after 2 Gy irradiation, and an increased number of fused giant osteoclasts and enhanced F-actin ring formation were observed. Consistently, the bone resorption activity and the enzyme expression of TRAP, cathepsin K, matrix metalloproteinase 9, activator protein 1, and Caspase 9 were increased following irradiation with 2 Gy. Furthermore, intracellular ROS production and apoptosis of osteoclast precursors were increased.

Conclusions

Irradiation with 2 Gy inhibited the viability of osteoclast precursors, but increased osteoclastogenesis by enhancing cell fusion and increasing the secretion of lytic enzymes, which may be an important mechanism of radiation-induced bone loss.



中文翻译:

辐射通过调节RAW 264.7细胞和小鼠骨髓来源的巨噬细胞中的细胞骨架和裂解酶来改变破骨细胞的形成。

摘要

目的

本研究的目的是研究破骨细胞前体中辐射作用对破骨细胞形成的双重性,特别是对细胞骨架和裂解酶表达的双重影响。因此,本研究可为临床预防和治疗放射性骨丢失提供有用的参考。

材料和方法

将两种典型的破骨细胞前体,鼠RAW 264.7巨噬细胞和小鼠骨髓衍生的巨噬细胞(BMM)暴露于0.25–8 Gy的辐射下,随后研究了它们对细胞活力,TRAP活性和骨吸收的影响。此外,检查了破骨细胞中细胞骨架,细胞凋亡和裂解酶表达的变化,以阐明辐射对破骨细胞形成的双重性的分子机制。

结果

在有或没有RANKL的1-8 Gy辐射下处理的RAW 264.7细胞和BMM中,观察到形态学变化和活力受损。然而,在2 Gy照射后,破骨细胞的细胞融合趋势增强,并且观察到融合巨破骨细胞数量增加和F-肌动蛋白环形成增加。一致地,用2 Gy照射后,骨吸收活性和TRAP,组织蛋白酶K,基质金属蛋白酶9,激活蛋白1和半胱天冬酶9的酶表达增加。此外,破骨细胞前体的细胞内ROS产生和细胞凋亡增加。

结论

2 Gy辐射抑制破骨细胞前体的活力,但通过增强细胞融合和增加裂解酶的分泌来增加破骨细胞的生成,这可能是辐射引起的骨质流失的重要机制。

更新日期:2020-10-05
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