• Chengjie Xiong, Yong Huang, Hui Kang, Tonghui Zhang, Feng Xu, and Xianhua Cai.
• Orthopaedic Department, Wuhan General Hospital of Guangzhou Command, Wuhan, China.
• Spine. 2017 Jan 15; 42 (2): E61-E70.

Study DesignThe 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.ObjectiveTo study the effect of MIF-mediated CD74 dependent ERK1/2 activation on the CEP degeneration.Summary Of Background DataMIF-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.MethodsChondrocytes 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.ResultsERK1/2 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.ConclusionThese 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.Level Of EvidenceN/A.

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