Visceral adipose tissue-derived serine protease inhibitor inhibits interleukin-1β-induced catabolic and inflammatory responses in murine chondrocytes

Mol Med Rep. 2014 Oct;10(4):2191-7. doi: 10.3892/mmr.2014.2478. Epub 2014 Aug 11.

Abstract

Visceral adipose tissue-derived serine protease inhibitor (vaspin) is a newly identified member of the adipocytokine family, whose precise role in chondrocyte metabolism remains to be elucidated. The aim of the present study was to investigate the effect of vaspin on chondrocytes. The cell viability and the cytotoxicity of vaspin in chondrocytes were examined. Furthermore, the gene expression of matrix metalloproteinases-2 and -9, a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5 and cathepsin D was also examined, as well as the protein production of cyclooxygenase-2, prostaglandin E2 and inducible nitrous oxide synthase following treatment with different concentrations of vaspin in the absence or presence of interleukin-1-beta (IL-1β). In addition, the protein levels of the inhibitor of nuclear factor-κB (IκB-α) and the phosphorylation of nuclear factor kappa B (NF‑κB) were investigated. Vaspin was not able to stimulate the proliferation of chondrocytes and demonstrated no significant cytotoxic effect at concentrations of 10-500 ng/ml following coincubation for 24 and 48 h. However, vaspin inhibited IL-1β‑induced production of catabolic factors and inflammatory mediators in chondrocytes, and also suppressed the phosphorylation of NF‑κB and the degradation of IκB‑α. The data from the present study suggested that vaspin has a protective effect in chondrocyte metabolism and is an important factor in the pathophysiology of osteoarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / genetics
  • ADAM Proteins / metabolism
  • ADAMTS4 Protein
  • ADAMTS5 Protein
  • Adipokines / toxicity*
  • Animals
  • Cathepsin D / genetics
  • Cathepsin D / metabolism
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chondrocytes / cytology
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Cyclooxygenase 2 / metabolism
  • Dinoprostone / metabolism
  • I-kappa B Proteins / metabolism
  • Interleukin-1beta / pharmacology*
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Phosphorylation / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Serpins / toxicity*
  • Signal Transduction / drug effects

Substances

  • Adipokines
  • I-kappa B Proteins
  • Interleukin-1beta
  • NF-kappa B
  • Nfkbia protein, mouse
  • Nfkbia protein, rat
  • Serpins
  • vaspin protein, mouse
  • NF-KappaB Inhibitor alpha
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Cyclooxygenase 2
  • Ptgs2 protein, rat
  • Cathepsin D
  • ADAM Proteins
  • ADAMTS4 protein, rat
  • ADAMTS5 Protein
  • Adamts5 protein, rat
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • ADAMTS4 Protein
  • Dinoprostone