MicroRNA‑195‑5p inhibitor prevents the development of osteoarthritis by targeting REGγ

Yang Shu1, Junpeng Long2, Weixiong Guo3

  • 1Department of Orthopedics, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan, Hubei 430015, P.R. China.

Insights

MicroRNA-195-5p is upregulated in osteoarthritis (OA) and promotes inflammation and apoptosis. Inhibiting miR-195-5p protects against OA by regulating Wnt/β-catenin and NF-κB pathways.

Area of Science:

  • Biomedical research
  • Molecular biology
  • Cell biology

Background:

  • Osteoarthritis (OA) is a prevalent inflammatory joint disease.
  • MicroRNAs (miRNAs) are implicated in OA pathogenesis, but their specific roles are unclear.
  • miR-195-5p is a potential regulator in OA development.

Purpose of the Study:

  • Investigate the expression and function of miR-195-5p in OA.
  • Elucidate the underlying molecular mechanisms involving miR-195-5p in OA.
  • Determine the therapeutic potential of targeting miR-195-5p in OA.

Main Methods:

  • Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for miR-195-5p expression.
  • Luciferase reporter assay to confirm REGγ as a direct target of miR-195-5p.
  • Cellular assays (MTT, Annexin V/PI) and ELISA to assess cell viability, apoptosis, and inflammatory cytokine levels (IL-1β, IL-6, TNF-α) in lipopolysaccharide (LPS)-induced OA models.

Main Results:

  • miR-195-5p was significantly upregulated in OA cartilage and LPS-treated ATDC5 cells.
  • miR-195-5p directly targets REGγ.
  • Downregulation of miR-195-5p reversed LPS-induced inhibition of cell proliferation, enhanced apoptosis, and elevated inflammatory cytokine levels.
  • miR-195-5p inhibition suppressed Wnt/β-catenin pathway repression and NF-κB pathway activation.
  • REGγ silencing reversed the protective effects of the miR-195-5p inhibitor.

Conclusions:

  • miR-195-5p exacerbates OA by promoting chondrocyte apoptosis and inflammation.
  • Targeting miR-195-5p offers a protective role in OA via modulation of Wnt/β-catenin and NF-κB signaling pathways.
  • REGγ acts as a downstream mediator of miR-195-5p's effects in OA pathogenesis.

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