长非编码 RNA XIST 通过海绵吸附 miR-29b-3p 抑制烟酰胺 N-甲基转移酶来抑制骨髓间充质干细胞的分化，从而促进骨质疏松症的发生。

Long non-coding RNA XIST promotes osteoporosis by inhibiting the differentiation of bone marrow mesenchymal stem cell by sponging miR-29b-3p that suppresses nicotinamide N-methyltransferase.

机构信息

Department of Orthopedics Surgery, Affiliated Hospital of Jianghan University, Wuhan, China.

Department of Internal Schistosomiasis Ward, Wuhan Daishan Hospital, Wuhan, China.

出版信息

Bioengineered. 2021 Dec;12(1):6057-6069. doi: 10.1080/21655979.2021.1967711.

DOI:10.1080/21655979.2021.1967711

PMID:34486487

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8806730/

Abstract

Bone formation is important in the development of osteoporosis (OP). X-inactive specific transcript (XIST), a lncRNA, is involved in this process; however, mode of its action is not known. We compared the serum levels of XIST and miR-29b-3p among the patients with and without OP. In rat bone marrow mesenchymal stem cells (BMSCs), during osteogenic differentiation, XIST expression was detected first, followed by overexpression or suppression of miR-29b-3p and NNMT. Expression of osteogenic genes, ALP (electrochemical alkaline phosphatase) and RUNX2 (Runt-related transcription factor 2) were detected by RT-qPCR and western blots, and the calcium nodules in BMSCs were detected by staining. The relationships of XIST, miR-29b-3p, and NNMT were characterized by dual-luciferase reporter assay. Serum XIST was significantly upregulated in patients of OP. XIST downregulated the ALP and Runx2 levels and inhibited calcium nodules, whereas low expression of XIST reversed these events. MiR-29b-3p was inhibited by XIST sponge and lowered the levels of ALP, Runx2, and calcium nodules. NNMT was negatively regulated by miR-29b-3p, promoting the osteogenic differentiation of BMSCs. In conclusion, XIST is highly expressed in OP, and regulates NNMT by sponging miR-29b-3p to suppress the osteogenic differentiation of BMSCs.

摘要

骨形成在骨质疏松症（OP）的发展中很重要。X 失活特异性转录物（XIST）是一种长非编码 RNA，参与这一过程；然而，其作用方式尚不清楚。我们比较了有和没有 OP 的患者之间的血清 XIST 和 miR-29b-3p 水平。在大鼠骨髓间充质干细胞（BMSCs）中，在成骨分化过程中，首先检测到 XIST 表达，然后过表达或抑制 miR-29b-3p 和 NNMT。通过 RT-qPCR 和 Western blot 检测成骨基因 ALP（电化学碱性磷酸酶）和 RUNX2（Runt 相关转录因子 2）的表达，并通过染色检测 BMSCs 中的钙结节。通过双荧光素酶报告基因检测法研究了 XIST、miR-29b-3p 和 NNMT 之间的关系。OP 患者的血清 XIST 显著上调。XIST 下调 ALP 和 Runx2 水平并抑制钙结节，而 XIST 低表达则逆转了这些事件。XIST 海绵抑制 miR-29b-3p，降低 ALP、Runx2 和钙结节的水平。NNMT 受 miR-29b-3p 的负调控，促进 BMSCs 的成骨分化。总之，XIST 在 OP 中高表达，通过海绵 miR-29b-3p 调节 NNMT，抑制 BMSCs 的成骨分化。