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长链非编码 RNA ODSM 的靶向过表达可以调节体外和体内成骨细胞的功能。

Targeted overexpression of the long noncoding RNA ODSM can regulate osteoblast function in vitro and in vivo.

机构信息

The Key Laboratory of Aerospace Medicine, Ministry of Education, Air Force Medical University, Xi'an, 710032, Shaanxi, China.

State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, 100094, China.

出版信息

Cell Death Dis. 2020 Feb 18;11(2):133. doi: 10.1038/s41419-020-2325-3.

DOI:10.1038/s41419-020-2325-3
PMID:32071307
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7028725/
Abstract

Ameliorating bone loss caused by mechanical unloading is a substantial clinical challenge, and the role of noncoding RNAs in this process has attracted increasing attention. In this study, we found that the long noncoding RNA osteoblast differentiation-related lncRNA under simulated microgravity (lncRNA ODSM) could inhibit osteoblast apoptosis and promote osteoblast mineralization in vitro. The increased expression level of the lncRNA ODSM partially reduced apoptosis and promoted differentiation in MC3T3-E1 cells under microgravity unloading conditions, and the effect was partially dependent on miR-139-3p. LncRNA ODSM supplementation in hindlimb-unloaded mice caused a decrease in the number of apoptotic cells in bone tissue and an increase in osteoblast activity. Furthermore, targeted overexpression of the lncRNA ODSM in osteoblasts partially reversed bone loss induced by mechanical unloading at the microstructural and biomechanical levels. These findings are the first to suggest the potential value of the lncRNA ODSM in osteoporosis therapy and the treatment of pathological osteopenia.

摘要

改善机械去负荷引起的骨丢失是一个重大的临床挑战，非编码 RNA 在这一过程中的作用引起了越来越多的关注。在这项研究中，我们发现长链非编码 RNA 成骨细胞分化相关 lncRNA（lncRNA ODSM）可在体外抑制成骨细胞凋亡并促进成骨细胞矿化。lncRNA ODSM 的表达水平增加部分减轻了微重力去负荷条件下 MC3T3-E1 细胞中的凋亡，并部分依赖于 miR-139-3p。后肢去负荷小鼠中补充 lncRNA ODSM 可减少骨组织中凋亡细胞的数量并增加成骨细胞活性。此外，成骨细胞中 lncRNA ODSM 的靶向过表达部分逆转了机械去负荷引起的微观结构和生物力学水平的骨丢失。这些发现首次表明 lncRNA ODSM 在骨质疏松症治疗和病理性骨质疏松症治疗中的潜在价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1214/7028725/6efcec51fc49/41419_2020_2325_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1214/7028725/356139500d38/41419_2020_2325_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1214/7028725/6cf594daa3dd/41419_2020_2325_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1214/7028725/1c0aba3e7dce/41419_2020_2325_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1214/7028725/d8a133124623/41419_2020_2325_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1214/7028725/0cc7a9a611aa/41419_2020_2325_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1214/7028725/dd8d1f997d9c/41419_2020_2325_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1214/7028725/6efcec51fc49/41419_2020_2325_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1214/7028725/356139500d38/41419_2020_2325_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1214/7028725/6cf594daa3dd/41419_2020_2325_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1214/7028725/1c0aba3e7dce/41419_2020_2325_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1214/7028725/d8a133124623/41419_2020_2325_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1214/7028725/0cc7a9a611aa/41419_2020_2325_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1214/7028725/dd8d1f997d9c/41419_2020_2325_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1214/7028725/6efcec51fc49/41419_2020_2325_Fig7_HTML.jpg

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