PEP-1-SIRT2-induced matrix metalloproteinase-1 and -13 modulates type II collagen expression via ERK signaling in rabbit articular chondrocytes

Exp Cell Res. 2016 Nov 1;348(2):201-208. doi: 10.1016/j.yexcr.2016.09.024. Epub 2016 Sep 30.

Abstract

Matrix metalloproteinases (MMPs) are critical for the degradation of the extracellular matrix (ECM), which includes cartilage-specific collagen types I, II and XI. We previously found that PEP-1-sirtuin (SIRT)2 could induce dedifferentiation of articular chondrocytes; however, the underlying mechanisms remains unclear. We addressed this in the present study by examining the association between PEP-1-SIRT2 and the expression of MMP-1 and MMP-13 and type II collagen in rabbit articular chondrocytes. We found that PEP-1-SIRT2 increased MMP-1 and -13 expression in a dose- and time-dependent manner, as determined by western blotting. A similar trend in MMP-1 and -13 levels was observed in cultures during expansion to four passages. Pharmacological inhibition of MMP-1 and -13 blocked the PEP-1-SIRT2-induced decrease in type II collagen level. Phosphorylation of extracellular regulated kinase (ERK) was increased by PEP-1-SIRT2; however, treatment with the mitogen-activated protein kinase inhibitor PD98059 suppressed PEP-1-SIRT2-induced MMP-1 and -13 expression and dedifferentiation while restoring type II collagen expression in passage 2 cells. These results suggest that PEP-1-SIRT2 promotes MMP-induced dedifferentiation via ERK signaling in articular chondrocytes.

Keywords: Chondrocytes; ERK signaling; Matrix Metalloproteinases; PEP-1-SIRT2; Type II collagen.

MeSH terms

  • Animals
  • Cartilage, Articular / cytology*
  • Cell Dedifferentiation / drug effects
  • Chondrocytes / cytology
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism*
  • Collagen Type II / metabolism*
  • Cysteamine / analogs & derivatives*
  • Cysteamine / pharmacology
  • Enzyme Activation / drug effects
  • MAP Kinase Signaling System / drug effects*
  • Matrix Metalloproteinase 1 / metabolism*
  • Matrix Metalloproteinase 13 / metabolism*
  • Models, Biological
  • Peptides / pharmacology*
  • Rabbits
  • Sirtuin 2 / pharmacology*

Substances

  • Collagen Type II
  • Pep-1 peptide
  • Peptides
  • Cysteamine
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 1
  • Sirtuin 2