Propionibacterium acnes induces cartilaginous endplate degeneration by promoting MIF expression via the NF-\u03baB pathway

Ying Zhang,Yeting Lin,Haiyan Zhou,Binbin Lin,Yanyan Yuan,Yuting Wang

doi:10.1186/s13018-020-01714-6

Abstract

BackgroundPropionibacterium acnes (P. acnes) is a novel pathogenic factor that contributes to cartilaginous endplate (CEP) degeneration. However, the underlying mechanism of P. acnes-induced CEP degeneration remains unclear. The objective of this study is to investigate the underlying mechanism of P. acnes-induced CEP degeneration.MethodsWe first examined MIF expression in degenerated human CEP samples by immunohistochemistry. We developed a P. acnes-induced rat model and detected MIF expression using immunohistochemistry. Additionally, we investigated the mechanism of P. acnes-induced CEP degeneration in CEP cells using western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR).ResultsWe found that compared with the normal human CEP, the expression of MIF was increased in the degenerated human CEP. In a rat model, P. acnes induced CEP degeneration and upregulated MIF expression significantly. More importantly, we revealed the underlying mechanism of P. acnes-induced CEP degeneration in the rat CEP cells. Firstly, P. acnes induced the expression of MIF in a concentration-dependent manner. Then, MIF upregulated the expression of MMP-13 and promoted the secretion of IL-6 and IL-1β. Finally, P. acnes may promote MIF expression via NF-κB pathway rather than ERK1/2 pathway.ConclusionP. acnes-induced MIF expression via NF-κB pathway may be the underlying mechanism of CEP degeneration.

Highlights

Propionibacterium acnes (P. acnes) is a novel pathogenic factor that contributes to cartilaginous endplate (CEP) degeneration
The expression levels of Macrophage inhibition factor (MIF) (Fig. 1b) and matrix metalloproteinases (MMPs)-13 (Fig. 1c) were increased in the degenerated group, while the expression of CEP degeneration by regulating anabolic molecules (Col II) (Fig. 1d) was higher in the normal control group. These results prove that MIF is sharply increased in human degenerated CEP, indicating that increased MIF expression might accelerate human CEP degeneration
Changes in P. acnes-inoculated rat CEPs To elucidate the correlation between MIF and CEP degeneration by P. acnes infection, the bacteria were inoculated into the lumbar intervertebral discs of rats

Summary

Introduction

Propionibacterium acnes (P. acnes) is a novel pathogenic factor that contributes to cartilaginous endplate (CEP) degeneration. The objective of this study is to investigate the underlying mechanism of P. acnes-induced CEP degeneration. Intervertebral disc degeneration (IVDD) refers to the structural disruption and composition change of the intervertebral disc that can induce many common discogenic diseases, including spinal instability, disc herniation, and lower back pain [1]. These diseases affect people’s life and work and significantly increase the medical burden [2, 3]. P. acnes may be important in the pathogenesis of IVDD, and the underlying mechanism of P. acnes-induced IVDD is worth further study

Objectives

Methods

Results

Discussion

Conclusion