Blockade of IL-6 alleviates bone loss induced by modeled microgravity in mice

He Baorong; Yin Xinhua; Hao Dingjun; Zhang Xuefang; Zhang Zhen; Zhang Ke; Yang Xiaobin

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Blockade of IL-6 alleviates bone loss induced by modeled microgravity in mice

机译：封锁IL-6减轻了通过小鼠模拟的微疱疹诱导的骨质流失

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This study investigated the effects of blockade of IL-6 on bone loss induced by modeled microgravity (MG). Adult male mice were exposed to hind-limb suspension (HLS) and treated with IL-6-neutralizing antibody (IL-6 nAb) for 4 weeks. HLS in mice led to upregulation of IL-6 expression in both sera and femurs. IL-6 nAb treatment in HLS mice significantly alleviated bone loss, evidenced by increased bone mineral density of whole tibia, trabecular thickness and number, bone volume fraction of proximal tibiae, and ultimate load and stiffness of femoral diaphysis. IL-6 nAb treatment in HLS mice significantly enhanced levels of osteocalcin in sera and reduced levels of deoxypyridinoline. In MC3T3-E1 cells exposed to MG in vitro, IL-6 nAb treatment increased mRNA expression and activity of alkaline phosphatase, mRNA expression of osteopontin and runt-related transcription factor 2, and protein levels of osteoprotegerin and decreased protein levels of receptor activator of the NF-kappa B ligand. In RAW254.7 cells exposed to MG, IL-6 nAb treatment downregulated mRNA expression of cathepsin K and tartrate-resistant acid phosphatase (TRAP) and reduced numbers of TRAP-positive multinucleated osteoclasts. In conclusion, blockade of IL-6 alleviated the bone loss induced by MG.

机译：本研究探讨了阻断IL-6对模拟微重力（MG）引起的骨丢失的影响。成年雄性小鼠暴露于后肢悬吊（HLS）并用IL-6中和抗体（IL-6 nAb）治疗4周。小鼠的HLS导致血清和股骨中IL-6表达上调。IL-6 nAb治疗HLS小鼠显著减轻骨丢失，表现为整个胫骨的骨密度、骨小梁的厚度和数量、胫骨近端的骨体积分数、股骨干的极限载荷和刚度增加。IL-6 nAb治疗HLS小鼠可显著提高血清骨钙素水平，降低脱氧吡啶啉水平。在体外暴露于MG的MC3T3-E1细胞中，IL-6 nAb处理增加了碱性磷酸酶的mRNA表达和活性、骨桥蛋白和runt相关转录因子2的mRNA表达，以及骨保护素的蛋白质水平，并降低了NF-κB配体的受体激活剂的蛋白质水平。在第254行。7细胞暴露于MG、IL-6 nAb处理后，组织蛋白酶K和抗酒石酸酸性磷酸酶（TRAP）的mRNA表达下调，TRAP阳性多核破骨细胞数量减少。总之，阻断IL-6可以减轻MG引起的骨丢失。

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来源
《Canadian Journal of Physiology and Pharmacology》 |2020年第10期|共6页
作者
He Baorong; Yin Xinhua; Hao Dingjun; Zhang Xuefang; Zhang Zhen; Zhang Ke; Yang Xiaobin;
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Xi An Jiao Tong Univ Hong Hui Hosp Dept Spine Surg Xian 710054 Peoples R China;

Xi An Jiao Tong Univ Hong Hui Hosp Dept Spine Surg Xian 710054 Peoples R China;

Xi An Jiao Tong Univ Hong Hui Hosp Dept Spine Surg Xian 710054 Peoples R China;

Xi An Jiao Tong Univ Hong Hui Hosp Dept Spine Surg Xian 710054 Peoples R China;

Xi An Jiao Tong Univ Hong Hui Hosp Dept Spine Surg Xian 710054 Peoples R China;

Xi An Jiao Tong Univ Hong Hui Hosp Dept Spine Surg Xian 710054 Peoples R China;

Xi An Jiao Tong Univ Hong Hui Hosp Dept Spine Surg Xian 710054 Peoples R China;

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正文语种 eng
中图分类药理学;
关键词
microgravity; bone loss; IL-6; osteoblastogenesis; osteoclastogenesis;

机译：微匍匐;骨质损失;IL-6;骨质纤维发生;骨质细胞发生;

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1. Bone Loss Induced by Simulated Microgravity, Ionizing Radiation and/or Ultradian Rhythms in the Hindlimbs of Rats [J] . ZHANG Ya Nan, SHI Wen Gui, LI He, 生物医学与环境科学（英文版） . 2018,第002期
2. Osthole Protects Against Microgravity-induced Bone Loss Through Suppressing miR-34c Expression in Hindlimb Suspension Rats [J] . Feng Xiu, He Jinpeng, Hua Junrui, 中国科学院近代物理研究所和兰州重离子研究装置年报：英文版 . 2018,第001期
3. 3 - 79 Modeled Microgravity Influences on Acute Damage in Male Mice Reproductive Organs Induced by Carbon-ion Beams Irradiation [J] . Zhang Luwei, Liu Yang, Zhang Hong, 中国科学院近代物理研究所和兰州重离子研究装置年报：英文版 . 2010,第001期
4. Icariin prevents bone loss by inhibiting bone resorption and stabilizing bone biological apatite in a hindlimb suspension rodent model [J] . Jin-peng He, Xiu Feng, Ju-fang Wang, 中国药理学报：英文版 . 2018,第011期
5. Treatment of hydrogen molecule abates oxidative stress and alleviates bone loss induced by modeled microgravity in rats. [J] . Y Sun, F Shuang, D M Chen, Osteoporosis international: a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA . 2013,第3期

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6. Adenosine A1 receptors regulate bone resorption in mice: Adenosine A1 receptor blockade or deletion increases bone density and prevents ovariectomy-induced bone loss in adenosine A1 receptor–knockout mice [J] . Firas M. Kara, Stephen B. Doty, Adele Boskey, Arthritis & Rheumatism . 2010,第2期

机译：腺苷A1受体调节小鼠的骨吸收：腺苷A1受体的阻滞或缺失可增加骨密度，并防止卵巢切除术引起的腺苷A1受体敲除小鼠的骨质流失
7. Adenosine A1 receptors regulate bone resorption in mice: Adenosine A1 receptor blockade or deletion increases bone density and prevents ovariectomy-induced bone loss in adenosine A1 receptor-knockout mice [J] . KaraF.M., DotyS.B., BoskeyA., Arthritis and Rheumatism . 2010,第2期

机译：腺苷A1受体调节小鼠的骨吸收：腺苷A1受体的阻滞或缺失可增加骨骼密度，并防止卵巢切除术在腺苷A1受体敲除小鼠中引起的骨丢失
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机译：高静态磁场对小鼠微重力诱导骨质损失回收的影响
9. Mechanisms and countermeasures of microgravity-induced bone loss: In vitro and in vivo model systems. [D] . Saxena, Ritu. 2009

机译：微重力引起的骨丢失的机制和对策：体外和体内模型系统。
10. Treatment with soluble bone morphogenetic protein type 1A receptor fusion protein alleviates irradiation-induced bone loss in mice through increased bone formation and reduced bone resorption [O] . Shen Wang, Jie Li, Huabei Sun, 2020

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11. Adenosine A1receptors regulate bone resorption in mice: Adenosine A1receptor blockade or deletion increases bone density and prevents ovariectomy-induced bone loss in adenosine A1receptor-knockout mice [O] . Firas M. Kara, Stephen B. Doty, Adele Boskey, 2010

机译：Adenosine A1receptors调节小鼠的骨吸收：腺苷A1receptor阻断或缺失增加骨密度并防止卵巢切除诱导的腺苷A1recepor-kextout小鼠中的骨质流失
12. Prostaglandin E2 Alleviates Cyclosporin A-Induced Bone Loss in the Rat [R] . Katz, I. A., Jee, W. S. S., Joffe, I. I., 1992

机译：前列腺素E2减轻大鼠环孢菌素a诱导的骨丢失

Blockade of IL-6 alleviates bone loss induced by modeled microgravity in mice

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