Knockdown of Long Non-Coding RNA RP11-445H22.4 Alleviates LPS-Induced Injuries by Regulation of MiR-301a in...

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• Osteoarthritis (OA) is a degenerative joint disease where long non-coding RNAs (lncRNAs) are implicated.
• The specific role of lncRNA RP11-445H22.4 in OA pathogenesis remains largely unexplored.
• This study investigates the function of lncRNA RP11-445H22.4 in lipopolysaccharide (LPS)-induced OA cellular models.

Purpose of the Study:

• To elucidate the impact of lncRNA RP11-445H22.4 on lipopolysaccharide (LPS)-induced chondrocyte viability, apoptosis, and inflammation.
• To explore the molecular mechanisms underlying the action of lncRNA RP11-445H22.4 in osteoarthritis.

Main Methods:

• Human cartilage ATDC5 cells were transfected to modulate RP11-445H22.4, miR-301a, and CXCR4 expression, followed by LPS treatment.
• Cell viability, apoptosis, apoptosis-related factors, and inflammatory cytokines were assessed using CCK-8, flow cytometry, western blot, RT-qPCR, and ELISA.
• Dual-luciferase reporter assays and western blot analyses were employed to confirm molecular interactions and signaling pathways (NF-κB, MAPK/ERK).

Main Results:

• LPS exposure decreased cell viability, increased apoptosis, and elevated pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α).
• Inhibition of RP11-445H22.4 significantly ameliorated LPS-induced cellular damage, promoting viability and reducing apoptosis and inflammation.
• The RP11-445H22.4-miR-301a interaction was confirmed, with miR-301a targeting CXCR4, and CXCR4 silencing mimicked the protective effects of RP11-445H22.4 inhibition by suppressing LPS-activated NF-κB and MAPK/ERK pathways.

Conclusions:

• The lncRNA RP11-445H22.4-miR-301a-CXCR4 axis is a critical regulator in LPS-induced chondrocyte injury.
• This axis offers a potential therapeutic target for osteoarthritis.
• RP11-445H22.4 demonstrates a protective role in OA through the miR-301a/CXCR4 pathway.