Long Non-coding RNA DLEU1 Promotes Progression of Osteoarthritis via miR-492/TLR8 Axis

Title:Long Non-coding RNA DLEU1 Promotes Progression of Osteoarthritis via miR-492/TLR8 Axis

Volume: 25 Issue: 16

Author(s): Chenzhe Ni, Wanglin Zhang, Sai Qiu*, Hao Cheng*Chunhui Ma*

Affiliation:

• Department of Orthopaedics, Qidong People’s Hospital, Nantong University, Jiangsu, 226200, China

• Department of Orthopaedics, Qidong People’s Hospital, Nantong University, Jiangsu, 226200, China

• Department of Orthopaedics, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, 200080, China

Abstract:

Background: Long non-coding RNAs (LncRNAs) are generally reported to participate in the development of Osteoarthritis (OA) by acting as competing endogenous RNAs (ceRNAs). However, the molecular mechanism is largely unknown. This study aimed to investigate the possible mechanisms contributing to osteoarthritis (OA).

Methods: Four gene expression profiles from patients with OA were downloaded from a public database and integrated to screen important RNAs associated with OA. Differentially expressed (DE) lncRNAs, microRNAs (miRNAs), and mRNAs were filtered, and a ceRNA network was constructed. An in vitro OA model was established by treating chondrocytes with IL-1β. The expression levels of MMP-13, COL2A1, aggrecan, and RUNX2 were detected by qRT-PCR and western blot. Cell proliferation ability was detected by CCK-8 assay. Flow cytometry was used for apoptosis assay. A dual luciferase reporter gene was used to confirm the relationship between DLEU1, miR-492, and TLR8.

Results: An OA-related ceRNA network, including 11 pathways, 3 miRNAs, 7 lncRNAs, and 16 mRNAs, was constructed. DLEU1 and TLR8 were upregulated, and miR-492 was downregulated in IL-1β-induced chondrocytes. Overexpression of DLEU1 suppressed viability and promoted apoptosis and extracellular matrix (ECM) degradation in IL-1β induced chondrocytes. Luciferase reporter assay validated the regulatory relations among DLEU1, miR-492, and TLR8. Further study revealed that the effects of DLEU1 on chondrocytes could be reversed by miR-492.

Conclusion: DLEU1 may be responsible for the viability, apoptosis, and ECM degradation in OA via miR-492/TLR8 axis.

Cite this article as:

Ni Chenzhe, Zhang Wanglin, Qiu Sai*, Cheng Hao*, Ma Chunhui*, Long Non-coding RNA DLEU1 Promotes Progression of Osteoarthritis via miR-492/TLR8 Axis, Current Pharmaceutical Biotechnology 2024; 25 (16) . https://dx.doi.org/10.2174/0113892010275579240116061104