Expression of serglycin in human disc is increased in degenerated discs and up-regulated in vitro by exposure to IL-1ß or TNF-α

Abstract

We investigated whether the multifunctional intercellular proteoglycan, serglycin, is expressed in human intervertebral disc cells and assessed its localization. We also investigated expression levels of serglycin in human annulus fibrosus (annulus) cells exposed to IL-1ß and TNF-α, which are two proinflammatory cytokines that are expressed during disc degeneration. Immunolocalization of serglycin was common in many cells of the human annulus, but less common in the nucleus pulposus (nucleus). Both intracellular and cell membrane localization were observed. Annulus cells from Thompson grades III, IV and V degenerated discs exhibited a 4.69 fold up-regulation in serglycin expression vs. cells from healthier grades I and II discs. In monolayer annulus cell culture, cells from more degenerated discs exhibited a 9.4 fold up-regulation of serglycin expression compared to cells from healthier discs. Exposure of cultured cells to IL-1ß or TNF-α caused significant up-regulation of serglycin expression. We found that serglycin expression increased with increasing disc degeneration both in vivo and in vitro, and also increased with exposure in vitro to IL-1ß and TNF-α.

Key words:

• disc degeneration
• gene expression
• IL-1ß
• proinflammatory cytokines
• serglycin
• TNF-ßα

Acknowledgments

We thank Nury Steuerwald, Ph.D., and Judy Parsons in the Molecular Biology Core for expert technical assistance with microarray and analysis, Natalia Zinchenko for performing immunohistochemistry, and Gretchen Hoelscher and Emilio Marrero, Ph.D., for assistance with microarray gene expression analysis. We also thank Michael Cox for assistance with sand rat colony maintenance. We acknowledge the support of the Brooks Back Pain Research Endowment for general laboratory support.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.