Induces Intervertebral Disc Degeneration by Promoting iNOS/NO and COX-2/PGE Activation via the ROS-Dependent NF-B Pathway.

Accumulating evidence suggests that () is a novel pathogenic factor promoting intervertebral disc degeneration (IVDD). However, the underlying mechanisms by which induces IVDD have been unclear. In this study, we quantified the severity of IVDD, as well as the expressions of inducible nitric oxide synthase (iNOS)/nitric oxide (NO) and cyclooxygenase (COX-2)/prostaglandin (PGE) in human intervertebral discs (IVDs) infected with . Compared with -negative IVDs, -positive IVDs showed increased iNOS/NO and COX-2/PGE activity concomitant with more severe IVDD. In order to detect the potential correlation between iNOS/NO expression, COX-2/PGE expression, and IVDD, we developed a -induced IVDD rat model and found that the upregulation of iNOS/NO and COX-2/PGE was essential to the occurrence of -induced IVDD. This finding was supported by the fact that the inhibition of iNOS/NO and COX-2/PGE activity ameliorated IVDD significantly, as evidenced by restored aggrecan and collagen II expression both and . Mechanistically, we found that induced iNOS/NO and COX-2/PGE expressions via a reactive oxygen species- (ROS-) dependent NF-B cascade. Furthermore, NADPH oxidase participated in -induced ROS, iNOS/NO, and COX-2/PGE expressions. Overall, these findings further validated the involvement of in the pathology of IVDD and provided evidence that -induced iNOS/NO and COX-2/PGE activation via the ROS-dependent NF-B pathway is likely responsible for the pathology of IVDD.