文献类型：期刊文献

英文题名：Osthole ameliorates simulated microgravity-induced bone loss through down-regulation of miR-34c-5p

作者：Feng, Xiu[1,2,3];Zhou, Heng[1,2,3];Zhang, Yanan[1,2];Yang, Pengfei[1,2,3];Bai, Hao[1,2,3];Zhang, Tongshan[1,2,3];Hua, Junrui[1,2];Zhang, Liying[4];Liu, Yongqi[4];Xie, Xiaodong[5];He, Jinpeng[1,2,3];Wang, Jufang[1,2,3]

第一作者：Feng, Xiu

通信作者：He, JP[1];Wang, JF[1]

机构：[1]Chinese Acad Sci, Inst Modern Phys, Key Lab Space Radiobiol Gansu Prov, Lanzhou 730000, Peoples R China;[2]Chinese Acad Sci, Inst Modern Phys, CAS Key Lab Heavy Ion Radiat Biol & Med, Lanzhou 730000, Peoples R China;[3]Univ Chinese Acad Sci, Beijing 100049, Peoples R China;[4]Gansu Univ Tradit Chinese Med, Key Lab Transfer Dunhuang Med & Prov & Ministeria, Lanzhou 730000, Peoples R China;[5]Lanzhou Univ, Sch Basic Med Sci, Inst Genet, Lanzhou 730000, Peoples R China

第一机构：Chinese Acad Sci, Inst Modern Phys, Key Lab Space Radiobiol Gansu Prov, Lanzhou 730000, Peoples R China

通信机构：[1]corresponding author), Chinese Acad Sci, Inst Modern Phys, 509 Nanchang Rd, Lanzhou 730000, Peoples R China.

年份：2021

卷号：183

起止页码：141

外文期刊名：ACTA ASTRONAUTICA

收录：;EI(收录号：20211410160426);Scopus(收录号：2-s2.0-85103310138);WOS:【SCI-EXPANDED(收录号:WOS:000666595000014)】；

基金：This work was supported by grants from the National Natural Sciences Foundation of China (Nos. 31870851 and 81770879), the Science and Technology Research Project of Gansu Province (Nos. 145RTSA012 and 17JR5RA307), the International Science & Technology Cooperation Program of China (No. 2015DFR30940), and the Open Foundation of Key Laboratory for Transfer of Dunhuang Medicine at the Provincial and Ministerial Level (No. DHYX18-21).

语种：英文

外文关键词：Osthole; miR-34c-5p; Simulated microgravity; Bone loss

摘要：Bone loss severely threatens the heath of astronauts in long-term spaceflight and the effects of the developed countermeasures are limited. Emerging studies have revealed the positive role of osthole (OST) in induction of osteogenic differentiation and bone formation. In this study, the effects of OST on bone metabolism were investigated in osteoblasts and rats treated with random positioning machine and hindlimb unloading, respectively. The results showed that OST treatment promoted the cellular proliferation and elevated the expression levels of RUNX2 and BMP2 in osteoblasts under simulated microgravity. In addition, hindlimb unloading rats administered with OST (5 mg kg/d, i.g.) exhibited improved bone mass, bone strength, expression of bone formation markers (BALP and OCN), and decreased expression of bone resorption markers (CTX-1 and TRACP-5b) in serum compared with rats treated with placebo (0.9% saline). Notably, we found that miR-34c-5p expression level was significantly up-regulated when exposed to simulated microgravity both in vitro and in vivo, and suppression of miR-34c-5p by antagomiR in rats obviously rescued the damages of BMD and trabecular bone microstructures caused by simulated microgravity. Importantly, OST treatment reversed miR-34c-5p expression level in hindlimb unloading rats, and ectopic expression of miR-34c-5p by transfection of agomiR in osteoblasts treated with OST decreased the expression levels of bone formation genes COL1 alpha 1, RUNX2, and BMP2. Overall, these data suggest an undisclosed role for OST in regulating microgravity-induced bone loss via control of miR-34c-5p expression, which may help to countermeasure development to overcome bone loss in spaceflight.