Glutaredoxin 1 (GRX1) inhibits oxidative stress and apoptosis of chondrocytes by regulating CREB/HO-1 in osteoarthritis

Mol Immunol. 2017 Oct:90:211-218. doi: 10.1016/j.molimm.2017.08.006. Epub 2017 Aug 23.

Abstract

GRX1 (glutaredoxin1), a sulfhydryl disulfide oxidoreductase, is involved in many cellular processes, including anti-oxidation, anti-apoptosis, and regulation of cell differentiation. However, the role of GRX1 in the oxidative stress and apoptosis of osteoarthritis chondrocytes remains unclear, prompting the current study. Protein and mRNA expressions were measured by Western blot and RT-qPCR. Oxidative stress was detected by the measurement of MDA and SOD contents. Cells apoptosis were detected by Annexin V-FITC/PI and caspase-3 activity assays. We found that the mRNA and protein expressions of GRX1 were significantly down-regulated in osteoarthritis tissues and cells. GRX1 overexpression increased the mRNA and protein expression of CREB and HO-1. Meanwhile, GRX1 overexpression inhibited oxidative stress and apoptosis in osteoarthritis chondrocytes. Furthermore, we found that GRX1 overexpression regulated HO-1 by increasing CREB, and that HO-1 regulated oxidative stress and apoptosis in osteoarthritis chondrocytes. Thus, GRX1 overexpression constrains oxidative stress and apoptosis in osteoarthritis chondrocytes by regulating CREB/HO-1, providing a novel insight into the molecular mechanism and potential treatment of osteoarthritis.

Keywords: Apoptosis; CREB; GRX1; HO-1; Osteoarthritis chondrocytes; Oxidative stress.

MeSH terms

  • Aged
  • Apoptosis / physiology*
  • Cells, Cultured
  • Chondrocytes / pathology
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Female
  • Glutaredoxins / genetics
  • Glutaredoxins / metabolism*
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism*
  • Humans
  • Male
  • Malondialdehyde / metabolism
  • Middle Aged
  • Osteoarthritis / pathology*
  • Oxidation-Reduction
  • Oxidative Stress / physiology*
  • RNA, Messenger / biosynthesis
  • Superoxide Dismutase-1 / metabolism

Substances

  • CREB1 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • GLRX protein, human
  • Glutaredoxins
  • RNA, Messenger
  • Malondialdehyde
  • HMOX1 protein, human
  • Heme Oxygenase-1
  • Superoxide Dismutase-1