長期空間飛行中，由于失重導(dǎo)致的骨丟失位列航天員健康的各種風(fēng)險因素之首,。中國航天員科研訓(xùn)練中心航天醫(yī)學(xué)基礎(chǔ)與應(yīng)用國家重點實驗室李英賢研究團隊與香港浸會大學(xué),、軍事醫(yī)學(xué)科學(xué)院、301醫(yī)院以及暨南大學(xué)的相關(guān)研究單位團結(jié)協(xié)作,，在失重性骨丟失研究領(lǐng)域取得了世界級的突破性研究成果,，發(fā)現(xiàn)和闡釋了一個同時參與造成失重和增齡性成骨能力降低的小核酸的功能，并且在實驗中針對該小核酸開發(fā)的治療藥物成功防止了模擬失重和增齡導(dǎo)致的成骨能力下降以及骨丟失,。今天,，該研究成果在線發(fā)表于國際權(quán)威學(xué)術(shù)期刊《自然-醫(yī)學(xué)》。
空間骨丟失是制約人類進軍深空的瓶頸因素,，也是建設(shè)月球基地和探索火星之前必須解決的影響航天員安全健康的問題,。小核酸分子（microRNA）在發(fā)育、凋亡,、代謝以及人類疾病方面起著重要的調(diào)控作用,。李英賢研究團隊與301醫(yī)院骨科研究所、暨南大學(xué)臨床醫(yī)院等單位合作,，經(jīng)過3年的協(xié)作積累與統(tǒng)計分析，對參與骨發(fā)育調(diào)控的microRNA分子在大量臨床骨質(zhì)疏松樣本中進行了大規(guī)模的篩選與鑒定,。軍事醫(yī)學(xué)科學(xué)院賀福初院士的生物信息學(xué)研究團隊對這些數(shù)據(jù)進行了統(tǒng)計分析,，將研究目標鎖定在一個與成骨細胞的功能負相關(guān)的小核酸分子（microRNA-214）。這個小核酸分子可以調(diào)控成骨細胞的分化過程,，調(diào)控成骨細胞的礦化成骨能力,。在此基礎(chǔ)上，該團隊在體外合成了microRNA-214的特異性抑制劑,，借助于能夠靶向成骨細胞的核酸遞送系統(tǒng),，將microRNA-214分子抑制劑精確遞送到成骨細胞表面。
實驗數(shù)據(jù)表明,，以microRNA-214為靶點的靶向治療能顯著抑制了模擬失重所致的骨質(zhì)疏松和增齡性骨質(zhì)疏松,。該項研究成果對未來中國航天員在空間站長期駐留所導(dǎo)致的骨質(zhì)丟失的防護和逆轉(zhuǎn)老年人骨質(zhì)疏松邁出了堅實的一步。（生物谷Bioon.com）
doi:10.1038/nm.3026
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miR-214 targets ATF4 to inhibit bone formation
Xiaogang Wang, Baosheng Guo, Qi Li, Jiang Peng, Zhijun Yang, Aiyuan Wang, Dong Li, Zhibo Hou, Ke Lv, Guanghan Kan, Hongqing Cao, Heng Wu, Jinping Song, Xiaohua Pan, Qiao Sun, Shukuan Ling, Yuheng Li, Mu Zhu, Pengfei Zhang, Songlin Peng, Xiaoqing Xie, Tao Tang, An Hong, Zhaoxiang Bian, Yanqiang Bai, Aiping Lu, Yinghui Li, Fuchu He, Ge Zhang & Yingxian Li
Emerging evidence indicates that microRNAs (miRNAs) have important roles in regulating osteogenic differentiation and bone formation. Thus far, no study has established the pathophysiological role for miRNAs identified in human osteoporotic bone specimens. Here we found that elevated miR-214 levels correlated with a lower degree of bone formation in bone specimens from aged patients with fractures. We also found that osteoblast-specific manipulation of miR-214 levels by miR-214 antagomir treatment in miR-214 transgenic, ovariectomized, or hindlimb-unloaded mice revealed an inhibitory role of miR-214 in regulating bone formation. Further, in vitro osteoblast activity and matrix mineralization were promoted by antagomir-214 and decreased by agomir-214, and miR-214 directly targeted ATF4 to inhibit osteoblast activity. These data suggest that miR-214 has a crucial role in suppressing bone formation and that miR-214 inhibition in osteoblasts may be a potential anabolic strategy for ameliorating osteoporosis.
