MiR-503 Regulates Interleukin-1β-Induced Apoptosis, Inflammation and Extracellular Matrix Degradation by Targeting CXCL9 in Human Nucleus Pulposus Cells

Zhijian Jiao, Jiangrong Fan, Jun Chen

Article ID: 7451
Vol 37, Issue 8, 2023
DOI: https://doi.org/10.23812/j.biol.regul.homeost.agents.20233708.395
Received: 8 September 2023; Accepted: 8 September 2023; Available online: 8 September 2023; Issue release: 8 September 2023

Abstract

Background: To evaluate the effects of microRNA-503 (miR-503) on human nucleus pulposus cells (HNPCs) by targeting CXCL9 (CXC chemokine ligand 9) to regulate interleukin-1β (IL-1β) production. Methods: Enzyme-Linked Immunosorbent Assay (ELISA) and Quantitative Real-time PCR (qRT-PCR) assays were used to determine miR-503 and CXCL-9 levels in HNPCs treated with and without IL-1β. Efficacy of miR-503 on cell apoptosis, inflammation and extracellular matrix degradation was evaluated with in vitro experiments. To verify the target of miR-503 dual-luciferase reporter assay was performed. The miR-503/CXCL-9 regulatory axis in HNPCs was also assessed. Results: Low miR-503, collagen II and aggrecan, and high CXCL9 expression were detected in degenerative nucleus pulposus (NP) tissues and NP cells challenged by IL-1β. IL-1β treatment time-dependently suppressed cell viability and lowered miR-503 level in HNPCs. Conversely, miR-503 overexpression increased cell viability, but inhibited inflammation and cell apoptosis. The luciferase reporter assay identified CXCL9 as a miR-503 target. Moreover, miR-503 overexpression or transfection with si-CXCL9 decreased CXCL9 in HNPCs expression. Notably, blocking CXCL9 expression reversed the damage induced by IL-1β. Conclusions: This study suggests that miR-503 may restrain apoptosis, inflammation and extracellular matrix degradation in intervertebral disc degeneration (IDD) by targeting CXCL9.


Keywords

intervertebral disc degeneration;miR-503;CXCL9;IL-1β;nucleus pulposus


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