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Int J Clin Exp Pathol 2013;6(11):2376-2385

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

Zhen Sun, Zhong-Yuan Wan, Yun-Shan Guo, Hai-Qiang Wang, Zhuo-Jing Luo

Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi’an, China. Equal contributors.

Received August 27, 2013; Accepted September 30, 2013; Epub October 15, 2013; Published November 1, 2013

Abstract: 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. (IJCEP1308065).

Keywords: Intervertebral disc, nucleus pulposus, vascular endothelial cells, FasL, Fas, HMEC-1

Address correspondence to: Hai-Qiang Wang and Zhuo-Jing Luo, Department of Orthopaedics, Xijing Hospital, Fourth Military Medical
University, 127 Changle Western Road, Xi’an, China, 710032. Tel: +86 29 84775285; Fax: +86 29 84775285; E-mail: hqwang@fmmu.edu.cn
(Hai-Qiang Wang); zjluo@fmmu.edu.cn (Zhuo-Jing Luo)