• Sheng Cao, Yuan Ma, Houzhi Yang, Gan Luo, Haiyang Cheng, Xin Jin, and Tianwei Sun.
• Tianjin Medical University, Tianjin, China; Department of Spinal Surgery, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, China.
• World Neurosurg. 2023 Apr 1; 172: e52e61e52-e61.

BackgroundIntervertebral disc degeneration is a very common disease worldwide and the leading cause of low back pain. Long noncoding RNAs are novel players in intervertebral disc degeneration and have multiple functions. This study explored the role of long noncoding RNA HCG18 in regulating extracellular matrix (ECM) degradation in nucleus pulposus cells (NPCs) during intervertebral disc degeneration.MethodsNPCs were subjected to interleukin-1β to induce a degenerative model of NPCs. Cell viability was assessed using Cell Counting Kit-8 assay. Messenger RNA and protein expressions were examined by real-time quantitative polymerase chain reaction and Western blot. The location of HCG18 was determined by nucleocytoplasmic separation assay. The binding relationships between HCG18, MIR4306, and EPAS1 were verified by dual luciferase reporter gene assay and/or RNA immunoprecipitation assay.ResultsHCG18 was highly expressed in interleukin-1β-induced degenerated NPCs, which was associated with reduced collagen II and aggrecan expression and increased MMP-13 and ADAMTS-4 expression. HCG18 knockdown could remarkably inhibit ECM degradation in IL-1β-induced degenerated NPCs, while HCG18 overexpression had the opposite effect. Our molecular study further revealed that HCG18 could sponge MIR4306, and HCG18 knockdown could suppress ECM degradation in degenerated NPCs by elevating MIR4306 expression. In addition, EPAS1 was identified as the direct target of MIR4306. As expected, MIR4306 overexpression inhibited ECM degradation in degenerated NPCs by downregulating EPAS1.ConclusionsHCG18 promoted ECM degradation in degenerated NPCs via regulation of the MIR4306/EPAS1 axis.Copyright © 2022. Published by Elsevier Inc.

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