Macrophage Inhibition Factor-Mediated CD74 Signal Modulate Inflammation and Matrix Metabolism in the Degenerated Cartilage Endplate Chondrocytes by Activating Extracellular Signal Regulated Kinase 1/2.

Abstract

The macrophage inhibition factor (MIF)-mediated CD74 dependent extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation were associated with inflammatory activity and matrix metabolism in human degenerated cartilage endplate (CEP). Anabolic/catabolic factors in pathogenesis of CEP degeneration were evaluated. To study the effect of MIF-mediated CD74 dependent ERK1/2 activation on the CEP degeneration. MIF-CD74 signal is closely related to the CEP degeneration by inducing the secretion of inflammatory cytokines. ERK1/2-mediated inflammatory pathway also plays a crucial role in the intervertebral disc degeneration. The role of the ERK1/2 pathway in CEP chondrocytes response to MIF-CD74 signal has, however, not been fully elucidated. Chondrocytes were exposed to MIF, with or without ERK1/2 inhibition; CD74 interfered chondrocytes were also exposed to MIF, with or without ERK inhibition. mRNAs were isolated for real-time polymerase chain reaction measurement of gene expression. Western blotting was carried out to analyze the protein expression. ERK1/2 expression was significantly increased by MIF. MIF modulates metabolism in CEP chondrocytes and decreased by its inhibitor PD98059. ERK1/2 expression was significantly decreased by CD74siRNA. Inflammatory cytokines expression was significantly increased by MIF-induced ERK1/2 activation and significantly suppressed by PD98059. On the contrary, matrix expression was significantly decreased by MIF-induced ERK1/2 activation and reversed by PD98059. CD74siRNA decreased the CD74 expression in chondrocytes. Inflammatory cytokines and matrix expression were not induced by MIF in CD74 interfered chondrocytes. These results show that MIF-CD74 signal elicits an imbalance between anabolic and catabolic metabolism in CEP chondrocytes via ERK signal pathway. ERK inhibition could exert therapeutic effect against the harmful effects of MIF-CD74 signal in CEP degeneration. N/A.