Increased Expression of Netrin-1 and its Deleted in Colorectal Cancer Receptor in Human Diseased Lumbar Intervertebral Disc Compared with Autopsy Control.

Abstract

Study Design. The expression of netrin-1 and its deleted in colorectal cancer (DCC) receptor were investigated in human lumbar discs using immunohistochemistry.Objective. To investigate the expression of netrin-1 and DCC receptor in human diseased and healthy lumbar intervertebral discs (IVDs) and to clarify the correlation between netrin-1 expression and the degree of neurovascular ingrowth.Summary of Background Data. Previous studies have showed neurovascular ingrowth into the inner regions of degenerated IVD, and suggested the ingrowth may contribute to discogenic low back pain. Netrin-1 is an axon guidance molecule which regulates axons seeking their final targets, and has been identified involved in a variety of pathological conditions, so is its DCC receptor. However, the role of netrin-1 in diseased IVDs remains unknown.Methods. Thirty-five diseased IVD specimens were collected from 34 patients with different lumbar diseases during posterior lumbar interbody fusion. 8 normal discs were obtained at autopsy as control. Using polyclonal or monoclonal antibody, the disc slides were immmunostained to detect the expression and distribution of netrin-1, the DCC, the neuronal marker(neurofilament), and the vascular endothelial cell marker(CD34).Results. Netrin-1 and DCC immunopositive cells distributed substantially from the annulus fibrosus (AF) to the nucleus pulposus (NP), and the immunopositivity was detected in the disc cells, endothelial cells and granulation tissue cells in the diseased discs. The percentage of netrin-1 positive disc cells of the NP was more than that of the AF. The expression of netrin-1 and DCC was weak in the normal discs. A significant positive correlation between the percentage of netrin-1 immunopositive disc cells and neurovascular scores was found.Conclusion. The increased expression of Netrin-1 and DCC in diseased IVDs compared with controls suggested they might play an important role in the process of neurovascular ingowth.