Dataset Information

Propionibacterium acnes Induces Intervertebral Disc Degeneration by Promoting iNOS/NO and COX-2/PGE₂ Activation via the ROS-Dependent NF-?B Pathway.

ABSTRACT: Accumulating evidence suggests that Propionibacterium acnes (P. acnes) is a novel pathogenic factor promoting intervertebral disc degeneration (IVDD). However, the underlying mechanisms by which P. acnes 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 P. acnes. Compared with P. acnes-negative IVDs, P. acnes-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 P. acnes-induced IVDD rat model and found that the upregulation of iNOS/NO and COX-2/PGE₂ was essential to the occurrence of P. acnes-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 in vivo and in vitro. Mechanistically, we found that P. acnes induced iNOS/NO and COX-2/PGE₂ expressions via a reactive oxygen species- (ROS-) dependent NF-?B cascade. Furthermore, NADPH oxidase participated in P. acnes-induced ROS, iNOS/NO, and COX-2/PGE₂ expressions. Overall, these findings further validated the involvement of P. acnes in the pathology of IVDD and provided evidence that P. acnes-induced iNOS/NO and COX-2/PGE₂ activation via the ROS-dependent NF-?B pathway is likely responsible for the pathology of IVDD.

SUBMITTER: Lin Y

PROVIDER: S-EPMC6120277 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Propionibacterium acnes Induces Intervertebral Disc Degeneration by Promoting iNOS/NO and COX-2/PGE2 Activation via the ROS-Dependent NF-κB Pathway.

Lin Yazhou Y Tang Guoqing G Jiao Yucheng Y Yuan Ye Y Zheng Yuehuan Y Chen Yong Y Xiao Jiaqi J Li Changwei C Chen Zhe Z Cao Peng P

Oxidative medicine and cellular longevity 20180819

Accumulating evidence suggests that Propionibacterium acnes (P. acnes) is a novel pathogenic factor promoting intervertebral disc degeneration (IVDD). However, the underlying mechanisms by which P. acnes 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 ...[more]

PMID: 30210652

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Project description:INTRODUCTION:Low back pain and vertebral endplate abnormalities are common conditions within the population. Subclinical infection caused by indolent pathogens can potentially lead to these findings, with differentiation between them notably challenging from a clinical perspective. Progressive infection of the intervertebral disc has been extensively associated with increasing low back pain, with Propionibacterium acnes specifically implicated with in relation to sciatica. The main purpose of this study is to identify if the presence of an infective pathogen within the intervertebral disc is primary or is a result of intraoperative contamination, and whether this correlates to low back pain. METHODS AND ANALYSIS:An open prospective cohort study will be performed. Subjects included within the study will be between the ages of 18 and 65 years and have a diagnosis of lumbar disc herniation requiring open decompression surgery. Excised herniated disc fragments, muscle and ligamentum flavum samples will be collected during surgery and sent to microbiology for tissue culture and pathogen identification. Score questionnaires for pain, functionality and quality of life will be given preoperatively and at 1, 3, 6 and 12 months postoperatively. A MRI will be performed 12 months after surgery for analysis of Modic changes and baseline comparison. The primary endpoint is the rate of disc infection in patients with symptomatic degenerative disc disease. The secondary endpoints will be performance scores, Modic incidence and volume. ETHICS AND DISSEMINATION:This study was approved by our Institutional Review Board and was only initiated after it (CAAE 65102617.2.0000.0071). Patients agreeing to participate will sign an informed consent form before entering the study. Results will be published in a peer reviewed medical journal irrespective of study findings. If shown to be the case, this would have profound effects on the way physicians treat chronic low back pain, even impacting health costs. TRIALS REGISTRATION NUMBER:NCT0315876; Pre-results.

Project description:BackgroundIn previous studies, Propionibacterium acnes was cultured from intervertebral disc tissue of ~25% of patients undergoing microdiscectomy, suggesting a possible link between chronic bacterial infection and disc degeneration. However, given the prominence of P. acnes as a skin commensal, such analyses often struggled to exclude the alternate possibility that these organisms represent perioperative microbiologic contamination. This investigation seeks to validate P. acnes prevalence in resected disc cultures, while providing microscopic evidence of P. acnes biofilm in the intervertebral discs.MethodsSpecimens from 368 patients undergoing microdiscectomy for disc herniation were divided into several fragments, one being homogenized, subjected to quantitative anaerobic culture, and assessed for bacterial growth, and a second fragment frozen for additional analyses. Colonies were identified by MALDI-TOF mass spectrometry and P. acnes phylotyping was conducted by multiplex PCR. For a sub-set of specimens, bacteria localization within the disc was assessed by microscopy using confocal laser scanning and FISH.ResultsBacteria were cultured from 162 discs (44%), including 119 cases (32.3%) with P. acnes. In 89 cases, P. acnes was cultured exclusively; in 30 cases, it was isolated in combination with other bacteria (primarily coagulase-negative Staphylococcus spp.) Among positive specimens, the median P. acnes bacterial burden was 350 CFU/g (12 - ~20,000 CFU/g). Thirty-eight P. acnes isolates were subjected to molecular sub-typing, identifying 4 of 6 defined phylogroups: IA1, IB, IC, and II. Eight culture-positive specimens were evaluated by fluorescence microscopy and revealed P. acnes in situ. Notably, these bacteria demonstrated a biofilm distribution within the disc matrix. P. acnes bacteria were more prevalent in males than females (39% vs. 23%, p = 0.0013).ConclusionsThis study confirms that P. acnes is prevalent in herniated disc tissue. Moreover, it provides the first visual evidence of P. acnes biofilms within such specimens, consistent with infection rather than microbiologic contamination.

Dataset Information

Propionibacterium acnes Induces Intervertebral Disc Degeneration by Promoting iNOS/NO and COX-2/PGE₂ Activation via the ROS-Dependent NF-?B Pathway.

Publications

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

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Dataset Information

Propionibacterium acnes Induces Intervertebral Disc Degeneration by Promoting iNOS/NO and COX-2/PGE2 Activation via the ROS-Dependent NF-?B Pathway.

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Propionibacterium acnes Induces Intervertebral Disc Degeneration by Promoting iNOS/NO and COX-2/PGE₂ Activation via the ROS-Dependent NF-?B Pathway.