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

被引:15
作者
Xiong, Chengjie [1 ]
Huang, Yong [1 ]
Kang, Hui [1 ]
Zhang, Tonghui [1 ]
Xu, Feng [1 ]
Cai, Xianhua [1 ]
机构
[1] Guangzhou Command, Wuhan Gen Hosp, Dept Orthopaed, 627 Wuluo Rd, Wuhan, Hubei, Peoples R China
关键词
cartilage endplate degeneration; CD74; extracellular signal-regulated kinase; inflammation; macrophage inhibition factor; MODIC TYPE-1; EXPRESSION; CELLS; PATHWAYS; DISEASE; ALPHA; MRI; ERK;
D O I
10.1097/BRS.0000000000001726
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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.
引用
收藏
页码:E61 / E70
页数:10
相关论文
共 24 条
  • [1] Macrophage migration inhibitory factor
    Baugh, JA
    Bucala, R
    [J]. CRITICAL CARE MEDICINE, 2002, 30 (01) : S27 - S35
  • [2] Macrophage migration inhibitory factor regulates interleukin-6 production by facilitating nuclear factor-kappa B activation during Vibrio vulnificus infection
    Chuang, Chia-Chang
    Chuang, Yin-Ching
    Chang, Wen-Teng
    Chen, Chi-Chung
    Hor, Lien-I
    Huang, A-Ming
    Choi, Pui-Ching
    Wang, Chi-Yun
    Tseng, Po-Chin
    Lin, Chiou-Feng
    [J]. BMC IMMUNOLOGY, 2010, 11
  • [3] Poly-l-Arginine Acts Synergistically with LPS to Promote the Release of IL-6 and IL-8 via p38/ERK Signaling Pathways in NCI-H292 Cells
    Fan, Xiao-Yun
    Chen, Bing
    Lu, Zhao-Shuang
    Jiang, Zi-Feng
    Zhang, Sheng-Quan
    [J]. INFLAMMATION, 2016, 39 (01) : 47 - 53
  • [4] Erk is essential for growth, differentiation, integrin expression, and cell function in human osteoblastic cells
    Lai, CF
    Chaudhary, L
    Fausto, A
    Halstead, LR
    Ory, DS
    Avioli, LV
    Cheng, SL
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (17) : 14443 - 14450
  • [5] Catabolic cytokine expression in degenerate and herniated human intervertebral discs:: IL-1β and TNFα expression profile
    Le Maitre, Christine Lyn
    Hoyland, Judith Alison
    Freemont, Anthony J.
    [J]. ARTHRITIS RESEARCH & THERAPY, 2007, 9 (04)
  • [6] Macrophage migration inhibitory factor
    Leng, L
    Bucala, R
    [J]. CRITICAL CARE MEDICINE, 2005, 33 (12) : S475 - S477
  • [7] MIF signal transduction initiated by binding to CD74
    Leng, L
    Metz, CN
    Fang, Y
    Xu, J
    Donnelly, S
    Baugh, J
    Delohery, T
    Chen, YB
    Mitchell, RA
    Bucala, R
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 197 (11) : 1467 - 1476
  • [8] Apoptotic Effect of Geniposide on Fibroblast-Like Synoviocytes in Rats with Adjuvant-Induced Arthritis via Inhibiting ERK Signal Pathway In Vitro
    Li, Rong
    Cai, Li
    Tang, Wen-jian
    Lei, Chao
    Hu, Cheng-mu
    Yu, Fang
    [J]. INFLAMMATION, 2016, 39 (01) : 30 - 38
  • [9] Degenerative disc disease of herniated intervertebral discs is associated with extracellular matrix remodeling, vimentin-positive cells and cell death
    Loreto, Carla
    Musumeci, Giuseppe
    Castorina, Alessandro
    Loreto, Corrado
    Martinez, Giuseppa
    [J]. ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER, 2011, 193 (02) : 156 - 162
  • [10] Macrophage migration inhibitory factor (MIF) promotes cell survival by activation of the Akt pathway and role for CSN5/JAB1 in the control of autocrine MIF activity
    Lue, H.
    Thiele, M.
    Franz, J.
    Dahl, E.
    Speckgens, S.
    Leng, L.
    Fingerle-Rowson, G.
    Bucala, R.
    Luscher, B.
    Bernhagen, J.
    [J]. ONCOGENE, 2007, 26 (35) : 5046 - 5059