Ionizing Radiation Activates Mitochondrial Function in Osteoclasts and Causes Bone Loss in Young Adult Male Mice.
Ionizing Radiation Activates Mitochondrial Function in Osteoclasts and Causes Bone Loss in Young Adult Male Mice.
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DOI：
10.3390/ijms23020675
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发表时间：
2022-01-08
影响因子：
5.6
通讯作者：
Kim HN
中科院分区：
文献类型：
--
作者：
Richardson KK;Ling W;Krager K;Fu Q;Byrum SD;Pathak R;Aykin-Burns N;Kim HN
电离辐射（IR）对骨量的破坏性影响在小鼠和人类中得到了充分的证明，最有可能是由于破骨细胞数量和功能增加。然而，导致骨细胞骨吸收不适当增加的机制仅部分了解。在这里，我们表明，暴露于多个部分的低剂量（10个部分的0.4戈伊全身照射[TBI]/周，即，分次暴露）和/或单次暴露于相同的总剂量4戈伊TBI引起年轻成年雄性小鼠的小梁骨质量而不是皮质骨质量的降低。这种破坏作用与高度活化的骨吸收有关。在暴露于分次或单一TBI的小鼠骨髓源性巨噬细胞培养物中，破骨细胞分化和成熟均增加。IR还增加了线粒体脱乙酰酶Sirtuin-3（Sirt 3）的表达和酶活性，Sirt 3是骨质疏松症发生过程中破骨细胞线粒体活性和骨吸收的必需蛋白。缺乏Sirt 3的破骨细胞祖细胞暴露于IR表现出受损的再吸收活性。总之，靶向破坏破骨细胞线粒体活性可能是IR诱导的骨丢失的一种新的治疗策略，Sirt 3可能是这种效应的主要介导剂。
The damaging effects of ionizing radiation (IR) on bone mass are well-documented in mice and humans and are most likely due to increased osteoclast number and function. However, the mechanisms leading to inappropriate increases in osteoclastic bone resorption are only partially understood. Here, we show that exposure to multiple fractions of low-doses (10 fractions of 0.4 Gy total body irradiation [TBI]/week, i.e., fractionated exposure) and/or a single exposure to the same total dose of 4 Gy TBI causes a decrease in trabecular, but not cortical, bone mass in young adult male mice. This damaging effect was associated with highly activated bone resorption. Both osteoclast differentiation and maturation increased in cultures of bone marrow-derived macrophages from mice exposed to either fractionated or singular TBI. IR also increased the expression and enzymatic activity of mitochondrial deacetylase Sirtuin-3 (Sirt3)—an essential protein for osteoclast mitochondrial activity and bone resorption in the development of osteoporosis. Osteoclast progenitors lacking Sirt3 exposed to IR exhibited impaired resorptive activity. Taken together, targeting impairment of osteoclast mitochondrial activity could be a novel therapeutic strategy for IR-induced bone loss, and Sirt3 is likely a major mediator of this effect.
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影响因子：
3.3
作者：
Ishii, Takeaki;Ito, Kazuo;Saito, Yasutoshi
通讯作者：
Saito, Yasutoshi
影响因子：
3.7
作者：
Hui SK;Sharkey L;Kidder LS;Zhang Y;Fairchild G;Coghill K;Xian CJ;Yee D
通讯作者：
Yee D
影响因子：
5.6
作者：
Kim HN;Richardson KK;Krager KJ;Ling W;Simmons P;Allen AR;Aykin-Burns N
通讯作者：
Aykin-Burns N
影响因子：
5.4
作者：
Khosla S;Monroe DG
通讯作者：
Monroe DG
DOI：
10.1089/jir.2014.0152
发表时间：
2015-06
期刊：
Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research
影响因子：
--
作者：
Alwood JS;Shahnazari M;Chicana B;Schreurs AS;Kumar A;Bartolini A;Shirazi-Fard Y;Globus RK
通讯作者：
Globus RK