MicroRNA-146a Ameliorates Inflammation via TRAF6/NF-κB Pathway in Intervertebral Disc Cells.
BACKGROUND Intervertebral disc degeneration (IDD) has been widely recognized as a major contributor to low back pain. Accumulating evidence suggests that IDD is linked to various pro-inflammatory cytokines and metabolites. Recently, numerous studies have demonstrated that microRNAs (miRNAs) play a pivotal role in the development of most disorders, including degenerative disc diseases. Previous reports have revealed that miRNA-146a (miR-146a) could attenuate neuropathic pain in the spinal cord. The aim of this study was to investigate the role of miR-146a in the inflammatory response of IDD. MATERIAL AND METHODS Quantitative real-time (RT)-PCR was performed to investigate the levels of miR-146a in the PBMCs (peripheral blood mononuclear cells) of patients with IDD. Human nucleus pulposus (NP) cells were transiently transfected with miR-146a mimic; control NP cell transfections lacked miR-146a. Then all NP cells were treated with LPS (10 μM) to induce inflammation. The mRNA levels of miR-146a in NP cells were determined by RT-PCR. In addition, the mRNA and protein expression levels of tumor necrosis factor (TNF), receptor-associated factor 6 (TRAF6), and nuclear factor (NF)-κB in NP cells were evaluated by quantitative RT-PCR and Western blot analysis, respectively. RESULTS We found that miR-146a was significantly downregulated in the PBMCs of patients. Moreover, overexpression of miR-146a significantly decreased the levels of pro-inflammatory cytokines in LPS-stimulated NP cells. The mRNA and protein levels of TRAF6 and NF-κB were downregulated by miR-146a overexpression. CONCLUSIONS These results suggest that overexpression of miR-146a could promote IDD through the TRAF/NF-κB pathway. Our findings also highlight miR-146a as a novel possible therapeutic target for IDD.
Department of Spine Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China (mainland).|Department of Orthopedics, Shandong Energy Zibo Mining Group Co. Ltd. Central Hospital, Zibo, Shandong, China (mainland).
Feng
F
Lv
Special Inspection Section, The Fifth People's Hospital of Zibo City, Zibo, Shandong, China (mainland).
Yingzi
Y
Huang
Department of Orthopedics, The Sixth People's Hospital of Zibo City, Zibo, Shandong, China (mainland).
Wentao
W
Lv
Department of Orthopedics, Shandong Energy Zibo Mining Group Co. Ltd. Central Hospital, Zibo, Shandong, China (mainland).
Longbiao
L
Yang
Special Inspection Section, The Fifth People's Hospital of Zibo City, Zibo, Shandong, China (mainland).
Feng
F
Li
Thyroid Disease Prevention and Control Center, ndemic Disease Control and Prevention Institute of Shandong Province, Jinan, Shandong, China (mainland).
Jingli
J
Fan
Department of Spine Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China (mainland).
Jianmin
J
Sun
D016022:Case-Control Studies; D002478:Cells, Cultured; D002681:China; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D055959:Intervertebral Disc Degeneration / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D035683:MicroRNAs / Q000008:administration & dosage / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D012333:RNA, Messenger; D048029:TNF Receptor-Associated Factor 6; C000604754:Tifab protein, human