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. Issue 2 (15th January 2017)

• Record Type: Journal Article
• Authors: Xiong, Chengjie; Huang, Yong; Kang, Hui; Zhang, Tonghui; Xu, Feng; Cai, Xianhua
• Is Part Of: Spine. Volume 42:Issue 2(2017)
• Publication Date: 2017-01-15
• Subjects: cartilage endplate degeneration -- CD74 -- extracellular signal–regulated kinase -- inflammation -- macrophage inhibition factor; Spine -- Abnormalities -- Periodicals; Spine -- Diseases -- Periodicals; Spine -- Surgery -- Periodicals; 616.73005
• DOI: 10.1097/BRS.0000000000001726
• Languages: English
• ISSNs: 0362-2436

Abstract

Abstract : Study Design: 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. Objective: To study the effect of MIF-mediated CD74 dependent ERK1/2 activation on the CEP degeneration. Summary of Background Data: 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. Methods: 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. Results: 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. Conclusion: 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. Level of Evidence: N/A