Abstract
Introduction
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.
Materials and Methods
The study groups consisted of NP from cadavers and patients as below: Normal cadaveric donors as control (n = 8; average age 41.8 ± 3.6 [range 37-47]) and patients with IDD undergoing discectomy as degenerative NP samples (n = 20; average age 43.4 ± 5.4 [range 35-52]). Here, we established a coculture system of human NP cells and vascular endothelial (HMEC-1) cells. In adition, upregulated FasL of NP cells were cocultured with HMEC-1 cells.
Results
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 upregulating 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. Moreover, we found an increased Fas expression in HMEC-1 cells following cocultured with NP cells, which might be closely linked with FasL produced by NP cells and enhance their interaction.
Conclusion
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.
None declared