Vascular endothelial growth factor-A is a survival factor for nucleus pulposus cells in the intervertebral disc

被引:118
作者
Fujita, Nobuyuki [1 ,2 ]
Imai, Jun-ichi [7 ]
Suzuki, Toru [1 ,2 ]
Yamada, Masayuki [6 ,8 ]
Ninomiya, Ken [1 ,2 ]
Miyamoto, Kana [1 ,2 ]
Iwasaki, Ryotaro [2 ,5 ]
Morioka, Hideo [1 ,4 ]
Matsumoto, Morio [1 ]
Chiba, Kazuhiro [1 ,4 ]
Watanabe, Shinya [7 ]
Suda, Toshio [2 ]
Toyama, Yoshiaki [1 ]
Miyamoto, Takeshi [1 ,2 ,3 ,4 ,9 ]
机构
[1] Keio Univ, Sch Med, Dept Orthoped Surg, Shinjuku Ku, Tokyo 1608582, Japan
[2] Keio Univ, Sch Med, Sakaguchi Lab,Dept Cell Differentiat, Shinjuku Ku, Tokyo 1608582, Japan
[3] Keio Univ, Sch Med, Dept Musculoskeletal Reconstruct & Regenerat Surg, Shinjuku Ku, Tokyo 1608582, Japan
[4] Keio Univ, Sch Med, Div Orthoped Res, Shinjuku Ku, Tokyo 1608582, Japan
[5] Keio Univ, Sch Med, Dept Dent & Oral Surg, Shinjuku Ku, Tokyo 1608582, Japan
[6] Keio Univ, Sch Med, Ctr Integrated Med Res, Shinjuku Ku, Tokyo 1608582, Japan
[7] Tokyo Med & Dent Univ, Dept Clin Informat, Bunkyo Ku, Tokyo 1138519, Japan
[8] Cent Inst Expt Anim, Biomed Res Dept, Kawasaki, Kanagawa, Japan
[9] Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol, Kawaguchi, Saitama 3320012, Japan
关键词
nucleus pulposus; vascular endothelial growth factor-A; intervertebral disc; avascular;
D O I
10.1016/j.bbrc.2008.05.044
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
The intervertebral disc (IVD) is composed of two avascular tissue types, the nucleus pulposus (NP) and the annulus fibrosus (AF). IVDs is the largest avascular tissue in the human body, however, how these tissues are maintained without a blood supply is poorly understood. Here we show that vascular endothelial growth factor-A (VEGF-A) is highly expressed in NP and that VEGF-A plays a role in NP survival. High VEGF-A expression in NP was detected by microarray analysis, and NP was positive for the hypoxic probe pimonidazole and hypoxia-responsive genes. VEGF-A expression in NP was promoted by hypoxic conditions in vitro. NP cells also expressed the membrane-bound VEGF receptor-1 (VEGFR-1), and the number of apoptotic cells in cultured cell model of NP increased following treatment with VEGFR-1-Fc, which traps VEGF-A in NP. These results indicate that NP is a hypoxic tissue, and that VEGF-A functions in NP survival in an autocrine/paracrine manner. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:367 / 372
页数:6
相关论文
共 23 条
[1]
Corneal avascularity is due to soluble VEGF receptor-1 [J].
Ambati, Balamurali K. ;
Nozaki, Miho ;
Singh, Nirbhai ;
Takeda, Atsunobu ;
Jani, Pooja D. ;
Suthar, Tushar ;
Albuquerque, Romulo J. C. ;
Richter, Elizabeth ;
Sakurai, Eiji ;
Newcomb, Michael T. ;
Kleinman, Mark E. ;
Caldwell, Ruth B. ;
Lin, Qing ;
Ogura, Yuichiro ;
Orecchia, Angela ;
Samuelson, Don A. ;
Agnew, Dalen W. ;
St. Leger, Judy ;
Green, W. Richard ;
Mahasreshti, Parameshwar J. ;
Curiel, David T. ;
Kwan, Donna ;
Marsh, Helene ;
Ikeda, Sakae ;
Leiper, Lucy J. ;
Collinson, J. Martin ;
Bogdanovich, Sasha ;
Khurana, Tejvir S. ;
Shibuya, Masabumi ;
Baldwin, Megan E. ;
Ferrara, Napoleone ;
Gerber, Hans-Peter ;
De Falco, Sandro ;
Witta, Jassir ;
Baffi, Judit Z. ;
Raisler, Brian J. ;
Ambati, Jayakrishna .
NATURE, 2006, 443 (7114) :993-997
[2]
An allele of COL9A2 associated with intervertebral disc disease [J].
Annunen, S ;
Paassilta, P ;
Lohiniva, J ;
Perälä, M ;
Pihlajamaa, T ;
Karppinen, J ;
Tervonen, O ;
Kröger, H ;
Lähde, S ;
Vanharanta, H ;
Ryhänen, L ;
Göring, HHH ;
Ott, J ;
Prockop, DJ ;
Ala-Kokko, L .
SCIENCE, 1999, 285 (5426) :409-412
[3]
Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1 [J].
Barleon, B ;
Sozzani, S ;
Zhou, D ;
Weich, HA ;
Mantovani, A ;
Marme, D .
BLOOD, 1996, 87 (08) :3336-3343
[4]
The effect of elevated intraocular oxygen on organelle degradation in embryonic chicken lens [J].
Bassnett, S ;
McNulty, R .
JOURNAL OF EXPERIMENTAL BIOLOGY, 2003, 206 (23) :4353-4361
[5]
Chondromodulin I is dispensable during enchondral ossification and eye development [J].
Brandau, O ;
Aszódi, A ;
Hunziker, EB ;
Neame, PJ ;
Vestweber, D ;
Fässler, R .
MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (18) :6627-6635
[6]
Metabolism of the extracellular matrix formed by intervertebral disc cells cultured in alginate [J].
Chiba, K ;
Andersson, GBJ ;
Masuda, K ;
Thonar, EJMA .
SPINE, 1997, 22 (24) :2885-2893
[7]
A hypoxia-driven vascular endothelial growth factor/Flt1 autocrine loop interacts with hypoxia-inducible factor-1α through mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 pathway in neuroblastoma [J].
Das, B ;
Yeger, H ;
Tsuchida, R ;
Torkin, R ;
Gee, MFW ;
Thorner, PS ;
Shibuya, M ;
Malkin, D ;
Baruchel, S .
CANCER RESEARCH, 2005, 65 (16) :7267-7275
[8]
2 MOLECULES RELATED TO THE VEGF RECEPTOR ARE EXPRESSED IN EARLY ENDOTHELIAL-CELLS DURING AVIAN EMBRYONIC-DEVELOPMENT [J].
EICHMANN, A ;
MARCELLE, C ;
BREANT, C ;
LEDOUARIN, NM .
MECHANISMS OF DEVELOPMENT, 1993, 42 (1-2) :33-48
[9]
CD24 is expressed specifically in the nucleus pulposus of intervertebral discs [J].
Fujita, N ;
Miyamoto, T ;
Imai, JI ;
Hosogane, N ;
Suzuki, T ;
Yagi, M ;
Morita, K ;
Ninomiya, K ;
Miyamoto, K ;
Takaishi, H ;
Matsumoto, M ;
Morioka, H ;
Yabe, H ;
Chiba, K ;
Watanabe, S ;
Toyama, Y ;
Suda, T .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 338 (04) :1890-1896
[10]
VEGF regulates haematopoietic stem cell survival by an internal autocrine loop mechanism [J].
Gerber, HP ;
Malik, AK ;
Solar, GP ;
Sherman, D ;
Liang, XH ;
Meng, G ;
Hong, K ;
Marsters, JC ;
Ferrara, N .
NATURE, 2002, 417 (6892) :954-958