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Updated: Oct 31, 2025

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation
Published on: March 15, 2018
LncRNA X inactive-specific transcript promotes osteoclast differentiation through Tgif2 by acting as a ceRNA of
Yuefeng Shao1,2, Xinya Hu3, Xuejian Wu1
1Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Abstract:
Aim: This study aims to investigate whether long noncoding RNA (lncRNA) X-inactive specific transcript (Xist) can regulate osteoclast differentiation in osteoporosis and the mechanism. Materials & methods: The mouse model of osteoporosis was established by ovariectomy surgery. Osteoclast differentiation from RAW264.7 cells was induced in vitro. The relationships between associated genes were assessed. Results:Xist and Tgif2 were upregulated, but miR-590-3p was downregulated in ovariectomy mouse femurs and cell models. Xist knockdown or miR-590-3p overexpression inhibited Tgif2 expression and osteoclast differentiation. Tgif2 and Xist were the targets of miR-590-3p. Increased miR-590-3p expression inhibited Tgif2 level and osteoclast differentiation, while Xist overexpression reversed these effects. Conclusion:Xist serves as a ceRNA of miR-590-3p to promote Tgif2 level; thereby, contributing to osteoclast differentiation.
Insights
Long noncoding RNA XIST promotes osteoclast differentiation in osteoporosis by acting as a ceRNA for miR-590-3p, upregulating Tgif2. This finding offers potential therapeutic targets for osteoporosis treatment.
Area of Science:
- Molecular Biology
- Cell Biology
- Bone Biology
Background:
- Osteoporosis is characterized by decreased bone mass and increased fracture risk.
- Osteoclast differentiation plays a critical role in bone resorption and osteoporosis pathogenesis.
- Long noncoding RNAs (lncRNAs) are emerging as key regulators in various biological processes, including bone metabolism.
Purpose of the Study:
- To investigate the role of long noncoding RNA X-inactive specific transcript (Xist) in regulating osteoclast differentiation in osteoporosis.
- To elucidate the underlying molecular mechanism involving Xist, miR-590-3p, and Tgif2.
Main Methods:
- Established a mouse model of osteoporosis via ovariectomy.
- Induced osteoclast differentiation from RAW264.7 cells in vitro.
- Assessed gene expression and regulatory relationships using molecular biology techniques.
Main Results:
- Xist and Tgif2 were upregulated, while miR-590-3p was downregulated in osteoporosis models.
- Xist knockdown or miR-590-3p overexpression inhibited Tgif2 expression and osteoclast differentiation.
- Xist functions as a competing endogenous RNA (ceRNA) for miR-590-3p, thereby promoting Tgif2 expression and osteoclast differentiation.
Conclusions:
- Xist promotes osteoclast differentiation in osteoporosis by sponging miR-590-3p and upregulating Tgif2.
- The Xist/miR-590-3p/Tgif2 axis represents a potential therapeutic target for osteoporosis.
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