title: Macrophage migration inhibitory factor inhibits the migration of cartilage end plate-derived stem cells by reacting with CD74.
abstract: BACKGROUND
  Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine that regulates inflammatory reactions and the pathophysiology of many inflammatory diseases. Intervertebral disc (IVD) degeneration is characterized by an inflammatory reaction, but the potential role of MIF in IVD degeneration has not been determined. Recent studies have shown that MIF and its receptor, CD74, are involved in regulating the migration of human mesenchymal stem cells (MSCs); Thus, MIF might impair the ability of mesenchymal stem cells (MSCs) to home to injured tissues. Our previous studies indicated that cartilage endplate (CEP)-derived stem cells (CESCs) as a type of MSCs exist in human degenerate IVDs. Here, we investigate the role of MIF in regulating the migration of CESCs.
  
  
  RESULTS
  CESCs were isolated and identified. We have shown that MIF was distributed in human degenerate IVD tissues and was subject to regulation by the pro-inflammatory cytokine TNF-α. Furthermore, in vitro cell migration assays revealed that nucleus pulposus (NP) cells inhibited the migration of CESCs in a number-dependent manner, and ELISA assays revealed that the amount of MIF in conditioned medium (CM) was significantly increased as a function of increasing cell number. Additionally, recombinant human MIF (r-MIF) inhibited the migration of CESCs in a dose-dependent manner. CESCs migration was restored when an antagonist of MIF, (S, R)-3(4-hydroxyphenyl)-4, 5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1), was added. Finally, a CD74 activating antibody (CD74Ab) was used to examine the effect of CD74 on CESCs motility and inhibited the migration of CESCs in a dose-dependent manner.
  
  
  CONCLUSIONS
  We have identified and characterized a novel regulatory mechanism governing cell migration during IVD degeneration. The results will benefit understanding of another possible mechanism for IVD degeneration, and might provide a new method to repair degenerate IVD by enhancing CESCs migration to degenerated NP tissues to exert their regenerative effects.
authors.affiliation: Department of Orthopedics, Xinqiao Hospital, Third Millitary Medical University, Chongqing, People's Repulic of China.
authors.forename: Cheng-jie
authors.initials: CJ
authors.lastname: Xiong
authors.forename: Bo
authors.initials: B
authors.lastname: Huang
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yan-ping
authors.initials: YP
authors.lastname: Cun
authors.forename: Lan-tao
authors.initials: LT
authors.lastname: Liu
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Chang-qing
authors.initials: CQ
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Pan
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
mesh_terms: D000368:Aged; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002356:Cartilage / Q000166:cytology*; D002465:Cell Movement / Q000187:drug effects; D055785:Gene Knockdown Techniques; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007403:Intervertebral Disc / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C462499:3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazoleacetic acid methyl ester; D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D007555:Isoxazoles; D008263:Macrophage Migration-Inhibitory Factors; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; C045084:invariant chain