Sinomenine Attenuates Cartilage Degeneration by Regulating miR-223-3p/NLRP3 Inflammasome Signaling

Inflammation. 2019 Aug;42(4):1265-1275. doi: 10.1007/s10753-019-00986-3.

Abstract

Sinomenine (SIN) has been shown to protect against IL-1β-induced chondrocyte apoptosis in vitro. However, the role of SIN in the anterior cruciate ligament transection (ACLT)-induced osteoarthritis (OA) mouse model and its underlying molecular mechanisms remain unclear. In the present study, the protective effect of SIN on ACLT-induced articular cartilage degeneration and IL-1β-induced chondrocyte apoptosis miR-223-3p/NLRP3 signaling regulation was investigated. Safranin O staining was performed to evaluate the pathological changes of articular cartilage. Chondrocyte apoptosis was measured with Annexin V-fluorescein isothiocyanate/polyimide (annexin V-FITC/PI) staining using flow cytometry. Gene and protein expression were detected by RT-qPCR and Western blotting, respectively. SIN administration markedly improved articular cartilage degradation in mice undergoing ACLT surgery. In addition, SIN treatment downregulated the levels of inflammatory cytokines and the protein expression of NLRP3 inflammasome components and upregulated the expression of miR-223-3p in OA mice and IL-1β-stimulated chondrocytes. In vitro, we found that NLRP3 was a direct target of miR-223-3p, and overexpression of miR-223-3p blocked IL-1β-induced apoptosis and the inflammatory response in chondrocytes. These findings indicate that miR-223-3p/NLRP3 signaling could be used as a potential target of SIN for the treatment of OA.

Keywords: NLRP3; chondrocyte; miR-223-3p; osteoarthritis; sinomenine.

MeSH terms

  • Animals
  • Antirheumatic Agents
  • Cartilage Diseases / prevention & control*
  • Cartilage, Articular / pathology*
  • Gene Expression Regulation
  • Inflammasomes / chemistry*
  • Mice
  • MicroRNAs / metabolism*
  • Morphinans / pharmacology*
  • Morphinans / therapeutic use
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Protective Agents
  • Signal Transduction

Substances

  • Antirheumatic Agents
  • Inflammasomes
  • MIRN223 microRNA, mouse
  • MicroRNAs
  • Morphinans
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Protective Agents
  • sinomenine