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

International Journal of Clinical and Experimental Pathology

Zhen Sun¹ 

关键词: Intervertebral disc;    nucleus pulposus;    vascular endothelial cells;    FasL;    Fas;    HMEC-1;   

DOI  :  

学科分类：生理学与病理学

来源: e-Century Publishing Corporation

【 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.

【 授权许可】

CC BY-NC