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长链非编码 RNA TCONS_00041960 通过靶向 miR-204-5p 和 miR-125a-3p 增强大鼠骨髓间充质干细胞的成骨分化并抑制其成脂分化。

Long non-coding RNA TCONS_00041960 enhances osteogenesis and inhibits adipogenesis of rat bone marrow mesenchymal stem cell by targeting miR-204-5p and miR-125a-3p.

机构信息

Department of Orthopaedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.

出版信息

J Cell Physiol. 2018 Aug;233(8):6041-6051. doi: 10.1002/jcp.26424. Epub 2018 Feb 28.

DOI:10.1002/jcp.26424
PMID:29319166
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5947671/
Abstract

A growing number of long non-coding RNAs (lncRNAs) have been found to be involved in diverse biological processes such as cell cycle regulation, embryonic development, and cell differentiation. However, limited knowledge is available concerning the underlying mechanisms of lncRNA functions. In this study, we found down-regulation of TCONS_00041960 during adipogenic and osteogenic differentiation of glucocorticoid-treated bone marrow mesenchymal stem cells (BMSCs). Furthermore, up-regulation of TCONS_00041960 promoted expression of osteogenic genes Runx2, osterix, and osteocalcin, and anti-adipogenic gene glucocorticoid-induced leucine zipper (GILZ). Conversely, expression of adipocyte-specific markers was decreased in the presence of over-expressed TCONS_00041960. Mechanistically, we determined that TCONS_00041960 as a competing endogenous RNA interacted with miR-204-5p and miR-125a-3p to regulate Runx2 and GILZ, respectively. Overall, we identified a new TCONS_00041960-miR-204-5p/miR-125a-3p-Runx2/GILZ axis involved in regulation of adipogenic and osteogenic differentiation of glucocorticoid-treated BMSCs.

摘要

越来越多的长链非编码 RNA（lncRNA）被发现参与多种生物学过程，如细胞周期调控、胚胎发育和细胞分化。然而，lncRNA 功能的潜在机制知之甚少。在这项研究中，我们发现在糖皮质激素处理的骨髓间充质干细胞（BMSCs）向成脂和成骨分化过程中，TCONS_00041960 的表达下调。此外，TCONS_00041960 的上调促进了成骨基因 Runx2、osterix 和骨钙素的表达，以及抗成脂基因糖皮质激素诱导的亮氨酸拉链（GILZ）的表达。相反，在过表达 TCONS_00041960 的情况下，脂肪细胞特异性标记物的表达减少。从机制上讲，我们确定 TCONS_00041960 作为一种竞争性内源性 RNA，与 miR-204-5p 和 miR-125a-3p 相互作用，分别调节 Runx2 和 GILZ。总的来说，我们鉴定了一个新的 TCONS_00041960-miR-204-5p/miR-125a-3p-Runx2/GILZ 轴，参与调节糖皮质激素处理的 BMSCs 的成脂和成骨分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0109/5947671/f533f4c44fd1/JCP-233-6041-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0109/5947671/bdb883a87508/JCP-233-6041-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0109/5947671/bc036364935d/JCP-233-6041-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0109/5947671/b67525bce8cc/JCP-233-6041-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0109/5947671/d3040911e1dd/JCP-233-6041-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0109/5947671/d3ce9a34905f/JCP-233-6041-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0109/5947671/f533f4c44fd1/JCP-233-6041-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0109/5947671/bdb883a87508/JCP-233-6041-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0109/5947671/bc036364935d/JCP-233-6041-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0109/5947671/b67525bce8cc/JCP-233-6041-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0109/5947671/d3040911e1dd/JCP-233-6041-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0109/5947671/d3ce9a34905f/JCP-233-6041-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0109/5947671/f533f4c44fd1/JCP-233-6041-g007.jpg

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