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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 1/2019

Open Access 01-12-2019 | Polymerase Chain Reaction | Research article

Upregulation of miR-107 expression following hyperbaric oxygen treatment suppresses HMGB1/RAGE signaling in degenerated human nucleus pulposus cells

Authors: Chi-Chien Niu, Song-Shu Lin, Li-Jen Yuan, Meng-Ling Lu, Steve W. N. Ueng, Chuen-Yung Yang, Tsung-Ting Tsai, Po-Liang Lai

Published in: Arthritis Research & Therapy | Issue 1/2019

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Abstract

Background

The expression of both high-mobility group box 1 (HMGB1) and receptor for advanced glycation end-products (RAGE) is upregulated in degenerated discs. HMGB1 is known to function as a coupling factor between hypoxia and inflammation in arthritis, and this inflammatory response is modulated by microRNAs (miRNAs), with miR-107 expression downregulated during hypoxia. In this study, we investigated the regulation of the miR-107/HMGB1/RAGE pathway in degenerated nucleus pulposus cells (NPCs) after hyperbaric oxygen (HBO) treatment.

Methods

NPCs were separated from human degenerated intervertebral disc tissues. The control cells were maintained in 5% CO2/95% air, and the hyperoxic cells were exposed to 100% O2 at 2.5 atmospheres absolute. MiRNA expression profiling was performed via microarray and confirmed by real-time PCR, and miRNA target genes were identified using bioinformatics and luciferase reporter assays. The cellular protein and mRNA levels of HMGB1, RAGE, and inducible nitric oxide synthase (iNOS) were assessed, and the phosphorylation of MAPK (p38MAPK, ERK, and JNK) was evaluated. Additionally, cytosolic and nuclear fractions of the IκBα and NF-κB p65 proteins were analyzed, and secreted HMGB1 and metalloprotease (MMP) levels in the conditioned media were quantified.

Results

Using microarray analyses, 96 miRNAs were identified as upregulated and 66 downregulated following HBO treatment. Based on these results, miR-107 was selected for further investigation. Bioinformatics analyses indicated that the 3′ untranslated region of the HMGB1 mRNA contained the “seed-matched-sequence” for hsa-miR-107, which was validated via dual-luciferase reporter assays. MiR-107 was markedly induced by HBO, and simultaneous suppression of HMGB1 was observed in NPCs. Knockdown of miR-107 resulted in upregulation of HMGB1 expression in HBO-treated cells, and HBO treatment downregulated the mRNA and protein levels of HMGB1, RAGE, and iNOS and the secretion of HMGB1. In addition, HBO treatment upregulated the protein levels of cytosolic IκBα and decreased the nuclear translocation of NF-κB in NPCs. Moreover, HBO treatment downregulated the phosphorylation of p38MAPK, ERK, and JNK and significantly decreased the secretion of MMP-3, MMP-9, and MMP-13.

Conclusions

HBO inhibits pathways related to HMGB1/RAGE signaling via upregulation of miR-107 expression in degenerated human NPCs.
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Metadata
Title
Upregulation of miR-107 expression following hyperbaric oxygen treatment suppresses HMGB1/RAGE signaling in degenerated human nucleus pulposus cells
Authors
Chi-Chien Niu
Song-Shu Lin
Li-Jen Yuan
Meng-Ling Lu
Steve W. N. Ueng
Chuen-Yung Yang
Tsung-Ting Tsai
Po-Liang Lai
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2019
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-019-1830-1

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