The role of MCP-1-CCR2 ligand-receptor axis in chondrocyte degradation and disease progress in knee osteoarthritis

Biol Res. 2015 Nov 17:48:64. doi: 10.1186/s40659-015-0057-0.

Abstract

Background: Osteoarthritis (OA) is a common arthritic disease and multifactorial whole-joint disease. Interactions of chemokines and OA is inadequately documented.

Results: In vivo and in vitro studies were conducted to investigate monocyte chemoattractant protein 1 (MCP-1) and receptor chemokine (C-C motif) receptor 2 (CCR2) in chondrocyte degradation and cartilage degeneration. Chondrocytes from 16 OA patients and 6 normal controls were involved in this study. After stimulation of MCP-1, the expression of MCP-1 and CCR2 increased significantly (P < 0.001) and the expression of MMP-13 also increased (P < 0.05). MCP-1 stimulation also induced (or enhanced) the apoptosis of OA chondrocytes (P < 0.05). Additionally, the degradation of cartilage matrix markers (metalloproteinase 3 and 13, MMP3 and MMP13) in the culture medium of normal chondrocytes was also assessed. Furthermore, intra-articular injection of MCP-1 in mouse knees induced cartilage degradation and the CCR2 antagonist did not impede cartilage destroy in rats knees of monosodium iodoacetate (MIA) model.

Conclusions: The results of this study demonstrate that the MCP-1-CCR2 ligand-receptor axis plays a special role in the initiation and progression of OA pathology. Patients with ambiguous etiology can gain some insight from the MCP-1-CCR2 ligand-receptor axis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Aged
  • Animals
  • Apoptosis / physiology
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism*
  • Chondrocytes / enzymology
  • Chondrocytes / metabolism*
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fibroblasts / metabolism
  • Humans
  • In Vitro Techniques
  • Iodoacetic Acid
  • Male
  • Matrilin Proteins / metabolism
  • Matrix Metalloproteinase 13 / metabolism
  • Matrix Metalloproteinase 3 / metabolism
  • Mice, Inbred C57BL
  • Middle Aged
  • Osteoarthritis, Knee / physiopathology*
  • Rats, Sprague-Dawley
  • Receptors, CCR2 / antagonists & inhibitors
  • Receptors, CCR2 / genetics
  • Receptors, CCR2 / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Synovial Membrane / cytology
  • Young Adult

Substances

  • Chemokine CCL2
  • Matrilin Proteins
  • Receptors, CCR2
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 3
  • Iodoacetic Acid