Curcumin Prevents Osteoarthritis by Inhibiting the Activation of Inflammasome NLRP3

J Interferon Cytokine Res. 2017 Oct;37(10):449-455. doi: 10.1089/jir.2017.0069.

Abstract

Curcumin has shown protective potential on osteoarthritis. However, its effect on treatment of osteoarthritis remains elusive so far. This study aimed to determine whether curcumin could ameliorate osteoarthritis in vivo and the underline mechanisms. The mice subjected to destabilization of the medial meniscus (DMM) surgery were administered curcumin. Cartilage integrity was evaluated by immunohistological staining. Expression levels of inflammatory cytokines from mice arthrodial cartilage were detected. THP-1 cells were primed by lipopolysaccharide (LPS)/ATP to induce inflammation, followed by the addition of curcumin. The expression of proinflammatory cytokines was also detected. Moreover, the expression of pro-caspase-1, cleaved caspase-1, and NLRP3 inflammasome was examined. Administration of curcumin significantly reduced osteoarthritis disease progression in DMM model of osteoarthritis. Curcumin suppressed mRNA expression of proinflammatory mediators in arthrodial cartilage of mice subjected to surgery. In LPS- and ATP-induced THP-1 macrophage cells, curcumin significantly suppressed the expression of interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) at both RNA and protein levels. Compared to vehicle-treated controls, curcumin also showed remarkably increased pro-caspase-1 and decreased cleaved caspase-1. This study provides the first evidence that curcumin exerts protection on osteoarthritis by inhibition to the release of inflammasome NLRP3, leading to the downregulation of inflammatory cytokines.

Keywords: NLRP3 inflammasome; chondroprotection; curcumin; inflammatory cytokines; osteoarthritis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Apoptosis / drug effects
  • Biopsy
  • Caspase 1 / metabolism
  • Cell Line
  • Cell Proliferation / drug effects
  • Curcumin / pharmacology*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Inflammasomes / metabolism*
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides / adverse effects
  • Male
  • Mice
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Osteoarthritis / drug therapy
  • Osteoarthritis / etiology
  • Osteoarthritis / metabolism*
  • Osteoarthritis / pathology
  • Reactive Oxygen Species / metabolism

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Inflammasomes
  • Inflammation Mediators
  • Lipopolysaccharides
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Reactive Oxygen Species
  • Caspase 1
  • Curcumin