The Overexpression of NALP3 Inflammasome in Knee Osteoarthritis Is Associated with Synovial Membrane Prolidase and NADPH Oxidase 2

Oxid Med Cell Longev. 2016:2016:1472567. doi: 10.1155/2016/1472567. Epub 2016 Sep 29.

Abstract

Osteoarthritis is characterized by the presence of proinflammatory cytokines and reactive oxygen species. We aimed to clarify the role of prooxidant enzyme content at the synovial membrane level and how it correlates with the inflammatory process in patients with knee osteoarthritis (KOA). In synovial membranes from KOA patients and control group, we analyzed the protein content of prooxidant enzymes such as Nox2, xanthine oxidase (XO), and prolidase as well as the proinflammatory NALP3. Results show that protein content of prolidase and Nox2 increased 4.8- and 8.4-fold, respectively, and XO showed an increasing trend, while the NALP3 inflammasome increased 5.4-fold with respect to control group. Levels of prolidase and XO had a positive correlation between the levels of NALP3 and Nox2. By principal component analysis the protein expression pattern by study groups was evaluated. Three clusters were identified; protein expression patterns were higher for clusters two (prolidase) and three (XO and Nox2) between KOA patients and controls. Data suggest that prooxidant enzymes increase in synovial membrane of KOA patients and may contribute to the inflammatory state and degradation of the articular cartilage.

MeSH terms

  • Adult
  • Aged
  • Body Mass Index
  • Case-Control Studies
  • Cluster Analysis
  • Cytokines / metabolism
  • Dipeptidases / metabolism*
  • Female
  • Humans
  • Inflammasomes / metabolism*
  • Linear Models
  • Male
  • Membrane Glycoproteins / metabolism*
  • Middle Aged
  • NADPH Oxidase 2
  • NADPH Oxidases / metabolism*
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Osteoarthritis, Knee / metabolism
  • Osteoarthritis, Knee / pathology*
  • Principal Component Analysis
  • Reactive Oxygen Species / metabolism
  • Synovial Membrane / metabolism*
  • Up-Regulation / drug effects
  • Xanthine Oxidase / metabolism

Substances

  • Cytokines
  • Inflammasomes
  • Membrane Glycoproteins
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Reactive Oxygen Species
  • Xanthine Oxidase
  • CYBB protein, human
  • NADPH Oxidase 2
  • NADPH Oxidases
  • Dipeptidases
  • proline dipeptidase