Treatment with hydrogen molecules prevents RANKL-induced osteoclast differentiation associated with inhibition of ROS formation and inactivation of MAPK, AKT and NF-kappa B pathways in murine RAW264.7 cells
Treatment with hydrogen molecules prevents RANKL-induced osteoclast differentiation associated with inhibition of ROS formation and inactivation of MAPK, AKT and NF-kappa B pathways in murine RAW264.7 cells
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DOI：
10.1007/s00774-013-0530-1
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发表时间：
2014-09-01
影响因子：
3.3
通讯作者：
Ma, Xin
中科院分区：
文献类型：
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作者：
Li, Dong-Zhu;Zhang, Qing-Xiang;Ma, Xin
氢分子（H-2）的骨保护作用已在几种骨质疏松症模型中得到证实，但其潜在的分子机制尚不清楚。破骨细胞分化是骨质流失相关疾病发生的重要因素。在这项工作中，我们评估了H-2孵育对NF κ B配体受体激活剂（RANKL）诱导的破骨细胞分化的影响。我们发现用H-2处理可以阻止rankl诱导的RAW264.7细胞和bmp细胞的破骨细胞分化。H-2抑制RANKL刺激下BMMs形成吸收坑的能力。H-2降低了破骨细胞特异性标志物的mRNA水平，包括酒石酸抗性酸性磷酸酶、降钙素受体、组织蛋白酶K、金属蛋白酶-9、碳酸酐酶ii型和液泡型H+- atp酶。H-2降低细胞内活性氧（ROS）形成，抑制NADPH氧化酶活性，下调Rac1活性和Nox1表达，减少线粒体ROS形成，增强核因子e2相关因子2核易位和血红素加氧酶-1活性。此外，H-2处理可抑制rankl诱导的活化T细胞核因子c1和c-Fos的表达。此外，H-2抑制NF-kappa B的激活，降低p38、细胞外信号调节激酶、c- jun - n末端激酶和RANKL刺激的蛋白激酶B （AKT）的磷酸化。综上所述，氢分子通过抑制活性氧的形成和nf - κ B、丝裂原活化蛋白激酶和AKT通路的失活来阻止rankl诱导的破骨细胞分化。
The bone protective effects of the hydrogen molecule (H-2) have been demonstrated in several osteoporosis models while the underlying molecular mechanism has remained unclear. Osteoclast differentiation is an important factor related to the pathogenesis of bone-loss related diseases. In this work, we evaluated the effects of incubation with H-2 on receptor activator of NF kappa B ligand (RANKL)-induced osteoclast differentiation. We found that treatment with H-2 prevented RANKL-induced osteoclast differentiation in RAW264.7 cells and BMMs. Treatment with H-2 inhibits the ability to form resorption pits of BMMs stimulated by RANKL. Treatment with H-2 reduced mRNA levels of osteoclast-specific markers including tartrate resistant acid phosphatase, calcitonin receptor, cathepsin K, metalloproteinase-9, carbonic anhydrase typeII, and vacuolar-type H+-ATPase. Treatment with H-2 decreased intracellular reactive oxygen species (ROS) formation, suppressed NADPH oxidase activity, down-regulated Rac1 activity and Nox1 expression, reduced mitochondrial ROS formation, and enhanced nuclear factor E2-related factor 2 nuclear translocation and heme oxygenase-1 activity. In addition, treatment with H-2 suppressed RANKL-induced expression of nuclear factor of activated T cells c1 and c-Fos. Furthermore, treatment with H-2 suppressed NF-kappa B activation and reduced phosphorylation of p38, extracellular signal-regulated kinase, c-Jun-N-terminal kinase, and protein kinases B (AKT) stimulated with RANKL. In conclusion, hydrogen molecules prevented RANKL-induced osteoclast differentiation associated with inhibition of reactive oxygen species formation and inactivation of NF-kappa B, mitogen-activated protein kinase and AKT pathways.