MCP-1-CCR2 ligand-receptor axis in human chondrocyte degradation and disease progress in osteoarthritis

Abstract

Purpose: To investigate the role of (OA). Methods: Expression of the C-C chemokines monocyte chemoattractant protein 1 (MCP-1), and it's receptor CCR-2, was assessed in 16 OA patients and 6 normal controls, by reverse transcriptase-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA) on MCP-1 stimulated chondrocytes, and the apoptosis of the chondrocytes was detected by flow cytometry. While, the Expression of the markers, collagen I, V, IX, XI and Matrix metalloproteinases (MMP), of chondrocyte degeneration was assessed by ELISA. Finally, as to estimate the essentiality of MCP-1-CCR2 ligand-receptor axis in induce and maintain the pathologic features of OA, the CCR-2 antagonist (RS102895) was used to block the animal model of OA in rats induced by intra-articular injection of monoiodoacetate (MIA), and the joint degeneration was assessed with the OARSI cartilage degeneration score in histological assessments of the joints of the rats. Results: The MCP-1 itself enhanced the autocrine of MCP-1 in OA and normal human cartilage and the Expression of collagen I, V, IX, XI and Matrix metalloproteinases (MMP) increased after Stimulation of MCP-1. The MCP-1 also induced the apoptosis of normal and OA chondrocytes. The CCR-2 antagonist retarded the establishment of a monoiodoacetate (MIA)-induced animal model of OA in rats. Conclusions: The results of this study prove that the MCP-1-CCR2 ligand-receptor axis plays an important role in the progress of the OA's pathology. Inhibition of the MCP-1-CCR2 ligand-receptor axis may retard the pathological progress of human OA. And, we speculate that lots of OA patients that etiology is unclear can gain some cues from the MCP-1-CCR2 ligand-receptor axis, according to our present study.