Cortistatin is endogenous to the human intervertebral disc and exerts in vitro mitogenic effects on annulus cells and a downregulatory effect on TNF-α expression.

Abstract

Cortistatin (CST) is a recently discovered cyclic neuropeptide with biologic anti-inflammatory properties relevant to disc degeneration. To test whether CST is present in the disc tissue, whether its expression is influenced by tumor necrosis factor-α (TNF-α), and whether it influences cell proliferation. Institutional review board-approved study using immunohistochemistry on human disc tissue, in vitro annulus cultures to determine the effect of CST on cell proliferation, and the effect of TNF-α on CST gene expression. Discs from 12 subjects used for immunohistochemistry, four annulus specimens used for cell culture with proinflammatory cytokines, and 11 used for cell proliferation analyses. Immunohistochemical localization of CST, gene expression of CST, and cell proliferation analyses. Immunohistochemistry localized CST in disc tissue. Microarray analysis measured CST gene expression. Human annulus cells were exposed to CST for proliferation tests or cultured for the effect of TNF-α on CST expression. Standard statistical analyses were performed. Immunohistochemistry identified CST in outer annulus, inner annulus, and nucleus tissue. Annulus cells exposed to TNF-α revealed significantly lower CST expression (p=.013). Exposure to CST significantly increased proliferation. Quantitative real-time polymerase chain reaction also confirmed expression of CST in vitro. Data provide the first evidence that CST is present in the human disc. Addition of CST significantly increased cell proliferation. Cortistatin expression was significantly downregulated by TNF-α exposure in vitro. Findings suggest possible in vivo reduction of the anti-inflammatory actions of CST because of elevated proinflammatory cytokines during degenerating disc.