FasL on human nucleus pulposus cells prevents angiogenesis in the disc by inducing Fas-mediated apoptosis of vascular endothelial cells

被引:4
作者
Sun, Zhen [1 ]
Wan, Zhong-Yuan [1 ]
Guo, Yun-Shan [1 ]
Wang, Hai-Qiang [1 ]
Luo, Zhuo-Jing [1 ]
机构
[1] Fourth Mil Med Univ, Dept Orthopaed, Xijing Hosp, Xian 710032, Peoples R China
来源
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY | 2013年 / 6卷 / 11期
关键词
Intervertebral disc; nucleus pulposus; vascular endothelial cells; FasL; Fas; HMEC-1; HUMAN INTERVERTEBRAL DISC; LIGAND EXPRESSION; IMMUNE PRIVILEGE; CANCER-CELLS; BACK-PAIN; IN-VITRO; DEGENERATION; GROWTH; INNERVATION; MECHANISM;
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The intervertebral disc is the largest avascular organ in the human body. However, with the progress of intervertebral disc degeneration (IDD), the disc tends to be vascularized increasingly via angiogenesis. It is well established that both human nucleus pulposus (NP) cells and vascular endothelial cells express FasL and Fas. However, the issue remains open as to whether there are certain active mechanisms preventing angiogenesis in the disc via the FasL-Fas machinery. Here, we established a co-culture system of human NP cells and vascular endothelial (HMEC-1) cells. We found that normal NP cells were more capable of inducing apoptosis in HMEC-1 cells (14.2 +/- 3.4%) than degenerate NP cells (6.7 +/- 1.9%), p<0.05. By up-regulating the FasL expression in degenerate NP cells, we found that FasL played an essential role in the mediation of HMEC-1 cell apoptosis with the activation of downstream FADD and caspase-3. Furthermore, we found an increased Fas expression in HMEC-1 cells following co-cultured with NP cells, which might be closely linked with FasL produced by NP cells and enhance their interaction. Collectively, this is the first study showing FasL-Fas network might plays an important role in the molecular mechanisms of angiogenesis avoidance of human disc. Consequently, our findings might shed light on the pathogenesis in human IDD and provide a novel target for the treatment strategies for IDD.
引用
收藏
页码:2376 / 2385
页数:10
相关论文
共 40 条
  • [1] HMEC-1 - ESTABLISHMENT OF AN IMMORTALIZED HUMAN MICROVASCULAR ENDOTHELIAL-CELL LINE
    ADES, EW
    CANDAL, FJ
    SWERLICK, RA
    GEORGE, VG
    SUMMERS, S
    BOSSE, DC
    LAWLEY, TJ
    [J]. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1992, 99 (06) : 683 - 690
  • [2] Newly synthesized quinazolinone HMJ-38 suppresses angiogenetic responses and triggers human umbilical vein endothelial cell apoptosis through p53-modulated Fas/death receptor signaling
    Chiang, Jo-Hua
    Yang, Jai-Sing
    Lu, Chi-Cheng
    Hour, Mann-Jen
    Chang, Shu-Jen
    Lee, Tsung-Han
    Chung, Jing-Gung
    [J]. TOXICOLOGY AND APPLIED PHARMACOLOGY, 2013, 269 (02) : 150 - 162
  • [3] Depraetere V, 1997, Semin Immunol, V9, P93, DOI 10.1006/smim.1997.0062
  • [4] Nerve growth factor expression and innervation of the painful intervertebral disc
    Freemont, AJ
    Watkins, A
    Le Maitre, C
    Baird, P
    Jeziorska, M
    Knight, MTN
    Ross, ERS
    O'Brien, JP
    Hoyland, JA
    [J]. JOURNAL OF PATHOLOGY, 2002, 197 (03) : 286 - 292
  • [5] Vascular endothelial growth factor-A is a survival factor for nucleus pulposus cells in the intervertebral disc
    Fujita, Nobuyuki
    Imai, Jun-ichi
    Suzuki, Toru
    Yamada, Masayuki
    Ninomiya, Ken
    Miyamoto, Kana
    Iwasaki, Ryotaro
    Morioka, Hideo
    Matsumoto, Morio
    Chiba, Kazuhiro
    Watanabe, Shinya
    Suda, Toshio
    Toyama, Yoshiaki
    Miyamoto, Takeshi
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2008, 372 (02) : 367 - 372
  • [6] Double role of Fas ligand in the apoptosis of intervertebral disc cells in vitro
    Han, Dunfu
    Ding, Yue
    Liu, Shang-Li
    Wang, Gang
    Si, In-Cheong
    Wang, Xinguang
    Cui, Liyang
    Huang, Dongshang
    [J]. ACTA BIOCHIMICA ET BIOPHYSICA SINICA, 2009, 41 (11) : 938 - 947
  • [7] The pathogenesis of degeneration of the intervertebral disc and emerging therapies in the management of back pain
    Hughes, S. P. F.
    Freemont, A. J.
    Hukins, D. W. L.
    McGregor, A. H.
    Roberts, S.
    [J]. JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME, 2012, 94B (10): : 1298 - 1304
  • [8] Fas-ligand expression on nucleus pulposus begins in developing embryo
    Inui, Y
    Nishida, K
    Doita, M
    Takada, T
    Miyamoto, H
    Yoshiya, S
    Kurosaka, M
    [J]. SPINE, 2004, 29 (21) : 2365 - 2369
  • [9] Human intervertebral disc aggrecan inhibits endothelial cell adhesion and cell migration In Vitro
    Johnson, WEB
    Caterson, B
    Eisenstein, SM
    Roberts, S
    [J]. SPINE, 2005, 30 (10) : 1139 - 1147
  • [10] Fas ligand expression on human nucleus pulposus cells decreases with disc degeneration processes
    Kaneyama, Shuichi
    Nishida, Kotaro
    Takada, Toru
    Suzuki, Teppei
    Shimomura, Takatoshi
    Maeno, Koichiro
    Kurosaka, Masahiro
    Doita, Minoru
    [J]. JOURNAL OF ORTHOPAEDIC SCIENCE, 2008, 13 (02) : 130 - 135