Research Paper Volume 15, Issue 23 pp 13680—13692
Adiponectin inhibits LPS-induced nucleus pulposus cell pyroptosis through the miR-135a-5p/TXNIP signaling pathway
- 1 The First Affiliated Hospital, Orthopedic Center, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China
Received: August 7, 2023 Accepted: October 15, 2023 Published: December 2, 2023
https://doi.org/10.18632/aging.205226How to Cite
Copyright: © 2023 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Pyroptosis, a newly discovered programmed cell death process, is characterized by NLRP3 inflammasome activation and pro-inflammatory mediator release. Nucleus pulposus (NP) cell pyroptosis is an important cause of intervertebral disc degeneration (IDD). Adiponectin (APN) is an adipokine and has an anti-inflammatory effect. However, whether and how APN protects against NP cell pyroptosis remains unexplored. Our results showed that human degenerated NP tissue displayed a significant increase in the protein levels of NLRP3, caspase-1 and GSDMD-N. APN expression was down-regulated in human degenerated NP tissue and NP cells challenged with lipopolysaccharide (LPS). Lentivirus-mediated overexpression of APN increased miR-135a-5p levels, decreased thioredoxin-interacting protein (TXNIP) expression and its interaction with NLRP3, and inhibited pyroptosis in human NP cells stimulated with LPS. TXNIP was identified as a direct target of miR-135a-5p. The inhibitory effects of APN on pyroptosis were reversed by pretreatment with miR-135a-5p inhibitor or lentiviral vector expressing TXNIP in LPS-treated human NP cells. In summary, these data suggest that APN restrains LPS-induced pyroptosis through the miR-135a-5p/TXNIP signaling pathway in human NP cells. Increasing APN levels could be a new approach to retard IDD.
Abbreviations
IDD: intervertebral disc degeneration; IL: interleukin; NP: nucleus pulposus; APN: adiponectin; NLRP3: nucleotide-binding oligomerization domain-like receptor protein 3; LPS: lipopolysaccharide; miRNAs: microRNAs; TXNIP: thioredoxin-interacting protein; PI: propidium iodide; GSDMD-N: Gasdermin N-terminal fragment; LDH: lactate dehydrogenase.