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Andrographolide suppresses osteoarthritis progression by regulating circ_Rapgef1/miR-383-3p/NLRP3 signaling axis

Wei Yan1, Hong Yu1, Bo Liu2

  • 1Department of Bone and Joint Surgery, Wendeng Orthopaedic Hospital of Shandong Province, Shandong, China.

Transplant Immunology
|February 5, 2022
PubMed
Abstract

Insights

Andrographolide protects against osteoarthritis by reducing inflammation and promoting chondrocyte survival. However, circ_Rapgef1 interferes with these benefits by modulating the miR-383-3p/NLRP3 pathway.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Immunology

Background:

  • Andrographolide (AD) shows potential anti-arthritic effects by promoting chondrocyte proliferation and inhibiting apoptosis.
  • The precise molecular mechanisms of AD's protective role in osteoarthritis (OA) require further investigation.

Purpose of the Study:

  • To elucidate the molecular mechanism of Andrographolide (AD) in osteoarthritis (OA).
  • To investigate the role of circ_Rapgef1, miR-383-3p, and NLRP3 in AD's anti-arthritic effects.

Main Methods:

  • Osteoarthritis mouse and cell models were established using anterior cruciate ligament transection (ACLT) and lipopolysaccharide (LPS) stimulation, respectively.
  • Cell proliferation, apoptosis, and inflammatory cytokine levels were assessed using MTT, EdU, flow cytometry, and ELISA.
  • The interaction between circ_Rapgef1, miR-383-3p, and NLRP3 was analyzed using dual-luciferase reporter assays and gene silencing/overexpression techniques.

Main Results:

  • AD treatment reduced inflammation and protected chondrocytes from LPS-induced damage in OA models.
  • Overexpression of circ_Rapgef1 attenuated AD's protective effects in OA chondrocytes.
  • A novel axis, circ_Rapgef1/miR-383-3p/NLRP3, was identified, where circ_Rapgef1 upregulates NLRP3 by targeting miR-383-3p.

Conclusions:

  • Circ_Rapgef1 negatively impacts AD's therapeutic effects in OA by regulating the miR-383-3p/NLRP3 signaling pathway.
  • Targeting the circ_Rapgef1/miR-383-3p/NLRP3 axis may offer a novel therapeutic strategy for osteoarthritis.
Keywords:
AndrographolideLPSNLRP3Osteoarthritiscirc_Rapgef1miR-383-3p

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