Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, China.
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
Cell Death Dis. 2020 Sep 23;11(9):795. doi: 10.1038/s41419-020-03006-7.
Bone marrow-derived mesenchymal stem cells (BMSCs) in postmenopausal osteoporosis models exhibit loss of viability and multipotency. Identification of the differentially expressed RNAs in osteoporotic BMSCs could reveal the mechanisms underlying BMSC dysfunction under physiological conditions, which might improve stem cell therapy and tissue regeneration. In this study, we performed high-throughput RNA sequencing and showed that the novel long non-coding RNA (lncRNA) LNC_000052 and its co-expressed mRNA PIK3R1 were upregulated in osteoporotic BMSCs. Knockdown of LNC_000052 could promote BMSC proliferation, migration, osteogenesis, and inhibit apoptosis via the PI3K/Akt signaling pathway. We found that both LNC_000052 and PIK3R1 shared a miRNA target, miR-96-5p, which was downregulated in osteoporotic BMSCs. Their binding sites were confirmed by dual-luciferase assays. Downregulation of miR-96-5p could restrain the effects of LNC_000052 knockdown while upregulation of miR-96-5p together with LNC_000052 knockdown could improve the therapeutic effects of BMSCs. In summary, the LNC_000052-miR-96-5p-PIK3R1 axis led to dysfunction of osteoporotic BMSCs and might be a novel therapeutic target for stem cell therapy and tissue regeneration.
骨髓间充质干细胞（BMSCs）在绝经后骨质疏松模型中表现出活力和多能性丧失。鉴定骨质疏松症 BMSCs 中差异表达的 RNA 可以揭示生理条件下 BMSC 功能障碍的机制，这可能有助于改善干细胞治疗和组织再生。在这项研究中，我们进行了高通量 RNA 测序，结果表明新型长非编码 RNA（lncRNA）LNC_000052 及其共表达的 mRNA PIK3R1 在骨质疏松症 BMSCs 中上调。LNC_000052 的敲低可以通过 PI3K/Akt 信号通路促进 BMSC 的增殖、迁移、成骨和抑制凋亡。我们发现 LNC_000052 和 PIK3R1 共享一个 miRNA 靶标 miR-96-5p，其在骨质疏松症 BMSCs 中下调。通过双荧光素酶报告基因实验证实了它们的结合位点。miR-96-5p 的下调可以抑制 LNC_000052 敲低的作用，而上调 miR-96-5p 与 LNC_000052 敲低的联合作用可以提高 BMSCs 的治疗效果。总之，LNC_000052-miR-96-5p-PIK3R1 轴导致骨质疏松症 BMSCs 功能障碍，可能成为干细胞治疗和组织再生的新治疗靶点。
