Zinc Protects Articular Chondrocytes through Changes in Nrf2-Mediated Antioxidants, Cytokines and Matrix Metalloproteinases

Nutrients. 2018 Apr 11;10(4):471. doi: 10.3390/nu10040471.

Abstract

Osteoarthritis (OA) is an age-related degenerative joint disease characterized by high oxidative stress, chondrocyte death and cartilage damage. Zinc has been implicated in the antioxidant capacity of the cell, and its deficiency might inhibit chondrocyte proliferation. The present study examined the potential of zinc as a preventive supplement against OA using the in vitro chondrosarcoma cell line SW1353 and an in vivo Wistar rat model to mimic OA progress induced by monosodium iodoacetate (MIA). The results demonstrated that, in SW1353 cells, 5 μM MIA exposure increased oxidative stress and decreased the expression of GPx1 and Mn-SOD but still increased GSH levels and HO-1 expression and enhanced the expression of interleukin (IL)-10, IL-1β, and matrix metalloproteinase (MMP)-13. Zinc addition could block these changes. Besides, the expression of Nrf2 and phosphorylated (p)-Akt was dramatically increased, implicating the p-Akt/Nrf2 pathway in the effects of zinc on MIA-treated cells. A rat model achieved similar results as those of cell culture, and 1.6 mg/kg/day of zinc supplementation is sufficient to prevent OA progress, while 8.0 mg/kg/day of zinc supplementation does not have a better effect. These findings indicate that zinc supplementation exerts a preventive effect with respect to MIA-induced OA progress.

Keywords: antioxidant; cytokine; matrix metalloproteinase; osteoarthritis; zinc.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology*
  • Cartilage, Articular / drug effects*
  • Cartilage, Articular / enzymology
  • Cartilage, Articular / pathology
  • Cell Line, Tumor
  • Chondrocytes / drug effects*
  • Chondrocytes / enzymology
  • Chondrocytes / pathology
  • Cytoprotection
  • Heme Oxygenase-1 / metabolism
  • Humans
  • Interleukins / metabolism*
  • Male
  • Matrix Metalloproteinases / metabolism*
  • NF-E2-Related Factor 2 / metabolism*
  • Osteoarthritis / enzymology
  • Osteoarthritis / pathology
  • Osteoarthritis / prevention & control*
  • Oxidative Stress / drug effects
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Zinc Sulfate / pharmacology*

Substances

  • Antioxidants
  • Interleukins
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Nfe2l2 protein, rat
  • Zinc Sulfate
  • HMOX1 protein, human
  • Heme Oxygenase-1
  • Proto-Oncogene Proteins c-akt
  • Matrix Metalloproteinases