<i>Propionibacterium acnes</i> Induces Intervertebral Disc Degeneration by Promoting iNOS/NO and COX‐2/PGE₂ Activation via the ROS‐Dependent NF‐<i>κ</i>B Pathway

Abstract

Accumulating evidence suggests that <i>Propionibacterium acnes</i> (<i>P. acnes</i>) is a novel pathogenic factor promoting intervertebral disc degeneration (IVDD). However, the underlying mechanisms by which <i>P. acnes</i> 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 (PGE₂) in human intervertebral discs (IVDs) infected with <i>P. acnes</i>. Compared with <i>P. acnes</i>-negative IVDs, <i>P. acnes</i>-positive IVDs showed increased iNOS/NO and COX-2/PGE₂ activity concomitant with more severe IVDD. In order to detect the potential correlation between iNOS/NO expression, COX-2/PGE₂ expression, and IVDD, we developed a <i>P. acnes</i>-induced IVDD rat model and found that the upregulation of iNOS/NO and COX-2/PGE₂ was essential to the occurrence of <i>P. acnes</i>-induced IVDD. This finding was supported by the fact that the inhibition of iNOS/NO and COX-2/PGE₂ activity ameliorated IVDD significantly, as evidenced by restored aggrecan and collagen II expression both <i>in vivo</i> and <i>in vitro</i>. Mechanistically, we found that <i>P. acnes</i> induced iNOS/NO and COX-2/PGE₂ expressions via a reactive oxygen species- (ROS-) dependent NF-<i>κ</i>B cascade. Furthermore, NADPH oxidase participated in <i>P. acnes</i>-induced ROS, iNOS/NO, and COX-2/PGE₂ expressions. Overall, these findings further validated the involvement of <i>P. acnes</i> in the pathology of IVDD and provided evidence that <i>P. acnes</i>-induced iNOS/NO and COX-2/PGE₂ activation via the ROS-dependent NF-<i>κ</i>B pathway is likely responsible for the pathology of IVDD.