The long non-coding RNA maternally expressed 3-micorRNA-15a-5p axis is modulated by melatonin and prevents nucleus pulposus cell inflammation and apoptosis.

MEG3 intervertebral disc degeneration melanin melatonin nucleus pulposus cell

Journal

Basic & clinical pharmacology & toxicology
ISSN: 1742-7843
Titre abrégé: Basic Clin Pharmacol Toxicol
Pays: England
ID NLM: 101208422

Informations de publication

Date de publication:
Nov 2023
Historique:
revised: 05 05 2023
received: 20 02 2023
accepted: 28 08 2023
pubmed: 2 9 2023
medline: 2 9 2023
entrez: 2 9 2023
Statut: ppublish

Résumé

Nucleus pulposus (NP) cell apoptosis is regarded as a critical risk factor for intervertebral disc degeneration (IVDD). Melatonin exerts a protective role on NP cells. The study concentrates on the role and mechanism of lncRNA MEG3 in melatonin-mediated effects on NP cells. An in vitro IVDD model was constructed using IL-1β on human NP cells. qRT-PCR investigated MEG3, miR-15a-5p and PGC-1α mRNA levels in tissues and NP cells. IL-1β-treated NP cells subsequent to transfection, followed by melatonin treatment. NP cell proliferation, viability, apoptosis and inflammatory reactions were assayed. Western blot checked the profiles of PGC-1α, SIRT1 and NF-κB p65. Student's t-test or one-way analysis of variance (ANOVA) followed by Tukey's test was used for statistical tests. As indicated by the data, melatonin weakened NP cell inflammation and apoptosis and enhanced MEG3 expression. MEG3 expression was attenuated in IVDD tissues. MEG3 knockdown impaired the function of melatonin, which was, however, strengthened by miR-15a-5p knockdown. MEG3 targeted miR-15a-5p, which targeted PGC-1α and repressed the PGC-1α/SIRT1 pathway. Collectively, this study has disclosed that the MEG3-miR-15a-5p-PGC-1α/SIRT1 pathway modulated by melatonin can hamper NP cell apoptosis and inflammation elicited by IL-1β.

Identifiants

pubmed: 37658573
doi: 10.1111/bcpt.13939
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

603-619

Subventions

Organisme : Shanghai University of Medicine & Health Sciences
Organisme : Project of Science and Technology Commission of Shanghai Municipality
ID : 20Y11913300
Organisme : Project of Shanghai Pudong New Area Municipal Health Commission
ID : PW2022D-11
Organisme : Project of Shanghai Shen Kang Hospital Development Center
ID : SHDC12020118

Informations de copyright

© 2023 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.

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Auteurs

Chengyuan Zhang (C)

Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Yongjia Qiu (Y)

Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Feng Yuan (F)

Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

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