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

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Osteoarthritis (OA) pathogenesis involves long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs).
• The precise molecular mechanisms underlying lncRNA involvement in OA remain largely unelucidated.
• This study investigates the role of lncRNAs in OA development.

Purpose of the Study:

• To explore the molecular mechanisms of osteoarthritis (OA) development.
• To construct a competing endogenous RNA (ceRNA) network related to OA.
• To investigate the function of DLEU1 in OA pathogenesis.

Main Methods:

• Integrated gene expression profiles from OA patients to identify key RNAs.
• Constructed a ceRNA network and an in vitro OA model using IL-1β-treated chondrocytes.
• Assessed cell viability, apoptosis, extracellular matrix (ECM) degradation, and validated molecular interactions using qRT-PCR, western blot, CCK-8, flow cytometry, and dual luciferase reporter assays.

Main Results:

• An OA-related ceRNA network comprising 11 pathways, 3 miRNAs, 7 lncRNAs, and 16 mRNAs was established.
• DLEU1 and TLR8 were upregulated, while miR-492 was downregulated in IL-1β-induced chondrocytes.
• DLEU1 overexpression impaired chondrocyte viability, increased apoptosis, and promoted ECM degradation, effects reversible by miR-492, confirming the DLEU1/miR-492/TLR8 regulatory axis.

Conclusions:

• DLEU1 plays a significant role in regulating chondrocyte viability, apoptosis, and ECM degradation in OA.
• The miR-492/TLR8 axis is a key pathway through which DLEU1 exerts its effects in OA.
• DLEU1 represents a potential therapeutic target for osteoarthritis.