Chitosan oligosaccharides inhibit IL-1β-induced chondrocyte apoptosis via the P38 MAPK signaling pathway

Glycoconj J. 2016 Oct;33(5):735-44. doi: 10.1007/s10719-016-9667-1. Epub 2016 May 13.

Abstract

The preventive and therapeutic effects of chitosan oligosaccharides (COS) on osteoarthritis (OA) have been rarely investigated. In this study, the protective effects of COS against IL-1β-induced chondrocyte apoptosis were evaluated and the underlying mechanisms were elucidated. Results showed that COS not only inhibited cell apoptosis in a dose-dependent manner but also ameliorated IL-1β-induced nuclear chromatin damage and mitochondrial membrane potential in chondrocytes. In IL-1β-treated chondrocytes, COS downregulated the expression of Bax and caspase-3 but upregulated the expression of Bcl-2 by inhibiting the phosphorylated p38 mitogen-activated protein kinase (MAPK). COS inhibited the mRNA expression of inducible nitric oxide synthase (iNOS) and matrix metalloproteinase-13 (MMP-13) and enhanced the mRNA expression of the tissue inhibitor of metalloproteinase-1 (TIMP-1). These results suggested that COS effectively inhibits the IL-1β-induced apoptosis of chondrocytes by activating the p38 MAPK signaling pathway. COS may also be used as a unique biological agent to prevent and treat OA.

Keywords: Apoptosis; Chitosan oligosaccharide; Chondrocytes; Interleukin-1β; Matrix metalloproteinase; Osteoarthritis.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Chitosan / pharmacology*
  • Chondrocytes / metabolism*
  • Gene Expression Regulation / drug effects
  • Interleukin-1beta / biosynthesis*
  • MAP Kinase Signaling System / drug effects*
  • Matrix Metalloproteinase 13 / biosynthesis
  • Nitric Oxide Synthase Type II / biosynthesis
  • Oligosaccharides / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Inhibitor of Metalloproteinase-1 / biosynthesis
  • bcl-2-Associated X Protein / biosynthesis
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Bax protein, rat
  • Bcl2 protein, rat
  • IL1B protein, rat
  • Interleukin-1beta
  • Oligosaccharides
  • Proto-Oncogene Proteins c-bcl-2
  • TIMP1 protein, rat
  • Tissue Inhibitor of Metalloproteinase-1
  • bcl-2-Associated X Protein
  • Chitosan
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • p38 Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 13
  • Mmp13 protein, rat