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环状RNA GCLC通过调控miR-516b-5p/GNAS轴促进骨髓间充质干细胞的成骨分化。

Circular RNA GCLC promotes osteogenic differentiation of bone marrow mesenchymal stem cells via modulating miR-516b-5p/GNAS axis.

作者信息

Li An, Zhang Sheng, Zhang Jing, Peng Zhihua, Feng Qinghui

机构信息

Deparment of Orthopedics and Traumatology, The Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University, Guangzhou, 510000, China.

Medical Clinic, The Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University, Guangzhou, 510000, China.

出版信息

J Orthop Surg Res. 2025 Aug 8;20(1):749. doi: 10.1186/s13018-025-06115-1.

DOI:10.1186/s13018-025-06115-1

PMID:40781640

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12333199/

Abstract

OBJECTIVE

Osteoporosis (OP) is a systemic bone disease without effective treatment at present. The aim of this study is to explore the role of the circular RNA GCLC (circGCLC) in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs).

METHODS

The expression of circGCLC, miR-516b-5p, and the G protein alpha subunit (GNAS) was determined during osteogenic differentiation of BMSCs. Plasmid or oligonucleotide transfection was used to modify the expression levels of circGCLC, miR-516b-5p, and GNAS for assessing their effects on osteogenic differentiation ability, osteogenesis-related proteins, and MAPK signalling pathway-related proteins in BMSCs. The interactions among circGCLC, miR-516b-5p, and GNAS were also investigated.

RESULTS

During osteogenic differentiation of BMSCs, circGCLC and GNAS levels increased, whereas miR-516b-5p expression decreased. The knockdown of circGCLC inhibited osteogenic differentiation and MAPK signalling pathway activation in BMSCs. The increase in osteogenic differentiation that was induced by circGCLC upregulation was reversed by overexpressing miR-516b-5p. The inhibitory effects of circGCLC silencing on BMSC osteogenic differentiation were counteracted by GNAS upregulation. CircGCLC competitively bound to miR-516b-5p, mediating GNAS expression.

CONCLUSION

CircGCLC activates the MAPK signalling pathway by sponging miR-516b-5p, which mediates GNAS expression, thereby promoting the osteogenic differentiation of BMSCs.

摘要

目的

骨质疏松症（OP）是一种目前尚无有效治疗方法的全身性骨病。本研究旨在探讨环状RNA GCLC（circGCLC）在骨髓间充质干细胞（BMSC）成骨分化中的作用。

方法

在BMSC成骨分化过程中测定circGCLC、miR-516b-5p和G蛋白α亚基（GNAS）的表达。采用质粒或寡核苷酸转染来改变circGCLC、miR-516b-5p和GNAS的表达水平，以评估它们对BMSC成骨分化能力、成骨相关蛋白和丝裂原活化蛋白激酶（MAPK）信号通路相关蛋白的影响。还研究了circGCLC、miR-516b-5p和GNAS之间的相互作用。

结果

在BMSC成骨分化过程中，circGCLC和GNAS水平升高，而miR-516b-5p表达降低。敲低circGCLC可抑制BMSC的成骨分化和MAPK信号通路激活。过表达miR-516b-5p可逆转circGCLC上调诱导的成骨分化增加。上调GNAS可抵消circGCLC沉默对BMSC成骨分化的抑制作用。CircGCLC与miR-516b-5p竞争性结合，介导GNAS表达。