Department of Spine Surgery, Hong Hui Hospital, Xi'an Jiaotong University, Xi'an, 710054, China.
Can J Physiol Pharmacol. 2020 Oct;98(10):678-683. doi: 10.1139/cjpp-2019-0632. Epub 2020 Aug 13.
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-κB 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.
本研究探讨了阻断白细胞介素 6（IL-6）对模拟微重力（MG）引起的骨丢失的影响。成年雄性小鼠接受后肢悬吊（HLS）并接受 IL-6 中和抗体（IL-6 nAb）治疗 4 周。HLS 导致小鼠血清和股骨中 IL-6 表达上调。HLS 小鼠中 IL-6 nAb 治疗显著缓解了骨丢失，表现为全胫骨骨矿物质密度、小梁厚度和数量、胫骨近端骨体积分数以及股骨骨干的最终负荷和刚度增加。HLS 小鼠中 IL-6 nAb 治疗显著提高了血清骨钙素水平，并降低了脱氧吡啶啉水平。在体外暴露于 MG 的 MC3T3-E1 细胞中，IL-6 nAb 治疗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 表达以及骨保护素蛋白的水平，并降低了核因子-κB 配体受体激活物的蛋白水平。在暴露于 MG 的 RAW254.7 细胞中，IL-6 nAb 治疗下调了组织蛋白酶 K 和抗酒石酸酸性磷酸酶（TRAP）的 mRNA 表达，并减少了 TRAP 阳性多核破骨细胞的数量。总之，阻断 IL-6 缓解了 MG 引起的骨丢失。
