Knockdown of LINC01385 inhibits osteoarthritis progression by modulating the microRNA-140-3p/TLR4 axis
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Updated: Oct 19, 2025
Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
Zidong Wang1, Chuanwang Huang1, Cunju Zhao1
1Department of Orthopedic Surgery, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China.
Abstract:
Long non-coding (lnc) RNAs have been associated with osteoarthritis (OA) progression. The aim of the present study was to investigate the regulatory mechanism of lncRNA LINC01385 in OA in vitro. The mRNA expression level of LINC01385, microRNA(miR)-140-3p, and Toll-like receptor 4 (TLR4) was detected using reverse transcription-quantitative PCR, while ELISA was used to determine the concentration of different inflammatory factors [tumor necrosis factor-α (TNF-α), IL-6, and prostaglandin E2 (PGE2)]. The viability of human articular chondrocytes (HC-a) was measured using a MTT assay and western blot analysis was performed to quantify the protein expression level of TLR4. The associations between miR-140-3p and LINC01385/TLR4 were confirmed using a dual-luciferase reporter assay. LINC01385 mRNA expression level was increased in OA tissues and IL-1β-induced HC-a. LINC01385 knockdown and miR-140-3p mimics reduced the concentration of inflammatory factors in IL-1β-induced HC-a and promoted cell survival. In addition, it was confirmed that LINC01385 targeted miR-140-3p, while TLR4 was a target gene of miR-140-3p. Negative correlations between LINC01385 and miR-140-3p, and between miR-140-3p and TLR4 were observed in OA tissues. Low mRNA expression level of miR-140-3p and high protein expression level of TLR4 reversed the inhibitory effect of LINC01385 knockdown on the inflammatory responses of IL-1β-induced HC-a and exhibited a stimulating effect on cell viability. LINC01385 knockdown reduced the progression of OA by modulating the miR-140-3p/TLR4 axis in vitro; thus, LINC01385 may be a therapeutic target for OA.
Insights
Long non-coding RNA LINC01385 promotes osteoarthritis (OA) progression by targeting the microRNA-140-3p/Toll-like receptor 4 axis. Inhibiting LINC01385 may offer a novel therapeutic strategy for OA treatment.
Area of Science:
- Molecular Biology
- Biochemistry
- Genetics
Background:
- Osteoarthritis (OA) is a degenerative joint disease associated with altered long non-coding RNA (lncRNA) expression.
- LncRNAs play crucial roles in cellular processes, and their dysregulation is implicated in OA pathogenesis.
Purpose of the Study:
- To elucidate the regulatory mechanism of lncRNA LINC01385 in osteoarthritis (OA) in vitro.
- To investigate the potential of LINC01385 as a therapeutic target for OA.
Main Methods:
- Quantification of LINC01385, microRNA (miR)-140-3p, and Toll-like receptor 4 (TLR4) mRNA expression via reverse transcription-quantitative PCR.
- Enzyme-linked immunosorbent assay (ELISA) for inflammatory factors (TNF-α, IL-6, PGE2).
- MTT assay for cell viability and Western blot for TLR4 protein expression.
- Dual-luciferase reporter assays to confirm interactions between miR-140-3p and LINC01385/TLR4.
Main Results:
- LINC01385 expression was upregulated in OA tissues and IL-1β-induced human articular chondrocytes (HC-a).
- LINC01385 knockdown and miR-140-3p mimics decreased inflammatory factors and enhanced cell survival in IL-1β-induced HC-a.
- LINC01385 targets miR-140-3p, and miR-140-3p targets TLR4. LINC01385 knockdown ameliorated OA progression by modulating the miR-140-3p/TLR4 axis.
Conclusions:
- LINC01385 promotes OA progression in vitro by sponging miR-140-3p and consequently upregulating TLR4.
- The miR-140-3p/TLR4 axis is a key pathway regulated by LINC01385 in OA.
- LINC01385 represents a potential therapeutic target for osteoarthritis.
