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Updated: May 7, 2025
Treatment of Ligament Constructs with Exercise-conditioned Serum: A Translational Tissue Engineering Model
Published on: June 11, 2017
Epigenetic modification regulates the ligamentum flavum hypertrophy through miR-335-3p/SERPINE2/β-catenin signaling
Yongzhao Zhao1,2,3, Shuai Jiang1,2,3, Longting Chen1,2,3
1Department of Orthopaedics, Peking University Third Hospital, Peking University, No.49 NorthGarden Road, Haidian District, Beijing, 100191, Beijing, China.
Background:
Epigenetic modifications have been proved to play important roles in the spinal degenerative diseases. As a type of noncoding RNA, the microRNA (miRNA) is a vital class of regulatory factor in the epigenetic modifications, while the role of miRNAs in the regulation of epigenetic modifications in ligamentum flavum hypertrophy (LFH) has not been fully investigated.
Methods:
The miRNA sequencing analysis was used to explore the change of miRNA expression during the fibrosis of ligamentum flavum (LF) cells caused by the TGF-β1 (10 ng/ml). The downregulated miRNA miR-335-3p was selected to investigate its effects on the fibrosis of LF cells and explored the accurate relevant mechanisms.
Results:
A total of 21 miRNAs were differently expressed during the fibrosis of LF cells. The downregulated miR-335-3p was selected for further investigation. MiR-335-3p was distinctly downregulated in the LFH tissues compared to non-LFH tissues. Overexpression of miR-335-3p could inhibit the fibrosis of LF cells. Further research showed miR-335-3p prevented the fibrosis of LF cells via binding to the 3'-UTR of SERPINE2 to reduce the expression of SERPINE2. The increased SERPINE2 expression might promote the fibrosis of LF cells via the activation of β-catenin signaling pathway to promote the transcription of fibrosis-related genes (ACTA2 and COL3A1).
Conclusions:
Our results revealed that miR-335-3p prevented the fibrosis of LF cells via the epigenetic regulation of SERPINE2/β-catenin signaling pathway. The epigenetic regulator miR-335-3p might be a promising potential target for the treatment of LFH.
Insights
MicroRNA miR-335-3p inhibits ligamentum flavum hypertrophy (LFH) by epigenetically downregulating SERPINE2, offering a potential therapeutic target for LFH treatment.
Area of Science:
- Biochemistry
- Molecular Biology
- Epigenetics
Background:
- Spinal degenerative diseases involve epigenetic modifications.
- MicroRNAs (miRNAs) are key epigenetic regulators.
- The role of miRNAs in ligamentum flavum hypertrophy (LFH) requires further investigation.
Purpose of the Study:
- To investigate the role of miRNAs in LFH.
- To explore the specific function and mechanism of miR-335-3p in LFH.
- To identify potential therapeutic targets for LFH.
Main Methods:
- miRNA sequencing to analyze miRNA expression changes in fibrotic ligamentum flavum (LF) cells.
- Investigated the effects of downregulated miR-335-3p on LF cell fibrosis.
- Explored the molecular mechanisms involving SERPINE2 and the β-catenin signaling pathway.
Main Results:
- 21 miRNAs were differentially expressed in fibrotic LF cells.
- miR-335-3p was significantly downregulated in LFH tissues.
- Overexpression of miR-335-3p inhibited LF cell fibrosis by targeting SERPINE2.
- SERPINE2 promoted LFH via the β-catenin pathway, upregulating ACTA2 and COL3A1.
Conclusions:
- miR-335-3p prevents LF cell fibrosis through epigenetic regulation of the SERPINE2/β-catenin pathway.
- miR-335-3p is a potential therapeutic target for LFH treatment.
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