| 髓核细胞分泌神经鞘胚素参与椎间盘退变中病理性神经长入的机制研究 |
| The mechanism of nucleus pulposus cells derived artemin in the pathological nerve ingrowth during intervertebral disc degeneration |
| 投稿时间：2024-11-20 |
| DOI：10.3969/j.issn.1672-5972.2024.06.008 |
| 中文关键词: 椎间盘退变 盘源性疼痛 神经鞘胚素（ARTN） RUNX1 |
| 英文关键词:Intervertebral disc degeneration Discogenic pain Artemin RUNX1 |
| 基金项目:国家自然科学基金资助重点项目（82430077）；国家自然科学基金资助青年科学基金项目（82402847） |
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| 中文摘要: |
| 目的 探究神经鞘胚素（Artemin, ARTN）参与退变髓核细胞诱导病理性神经长入椎间盘的作用和机制。方法 收集不同退变等级的退变人髓核组织，检测人髓核组织中ARTN的表达情况；利用IL-1β构建大鼠髓核细胞炎性退变模型，检测髓核细胞中Artn的mRNA和蛋白质表达水平；取髓核细胞条件性培养基对背根神经元细胞系F11细胞进行间接共培养，检测神经元神经突的生长情况；炎性退变模型下敲低髓核细胞Artn表达，检测条件培养基对神经元神经突生长情况的影响；应用生物信息学预测Artn上游转录因子，并对潜在的转录调控机制进行探究。结果 重度退变人髓核组织中ARTN表达水平显著高于轻度退变人髓核组织；IL-1β显著上调大鼠原代髓核细胞Artn的mRNA和蛋白质表达水平；退变髓核细胞条件性培养基显著促进背根神经元细胞系F11细胞神经突的发生和生长，敲低髓核细胞Artn则显著弱化该效应；靶向抑制Artn上游转录因子RUNX1则可以显著逆转IL-1β的促进Artn表达作用。结论 IL-1β通过上调Runx1促进髓核细胞Artn转录，诱导神经元的神经突发生和生长，促进椎间盘退变过程中病理性神经长入。 |
| 英文摘要: |
| Objective To explore the role and mechanism of artemin (ARTN) in the pathological nerve ingrowth into the intervertebral disc, induced by degenerated nucleus pulposus cells.Methods We collected the degenerated human nucleus pulposus tissues with different Pfirrmann grades and detected the protein level of ARTN in human nucleus pulposus tissues. The inflammatory cytokine induced degeneration model of rat nucleus pulposus cells was constructed by using IL-1β, and the mRNA and protein expression levels of Artn in nucleus pulposus cells were evaluated. The conditional medium of the nucleus pulposus cells was extracted for co-culture with the dorsal root neuron cell line F11 to detect the growth of neuronal neurites. In the inflammatory cytokine induced degeneration model, the expression of Artn in nucleus pulposus cells was knocked down, and the effect of the conditional medium on neuritogenesis and neurite outgrowth was determined. Bioinformatics was used to predict the upstream transcription factors of Artn, and the potential transcriptional regulatory mechanism was explored.Results The expression level of ARTN in the degenerated human nucleus pulposus tissues with a higher Pfirrmann grade was significantly higher than that in the degenerated human nucleus pulposus tissues with a lower Pfirrmann grade. IL-1β significantly up-regulated the mRNA and protein expression levels of Artn in nucleus pulposus cells. The conditional medium of degenerated nucleus pulposus cells significantly promoted the neuritogenesis and growth of neurites in dorsal root neuron cell line F11. Knockdown of Artn in nucleus pulposus cells significantly attenuated this effect. Targeted inhibition of the upstream transcription factor RUNX1 of Artn could significantly reverse the promoting effect of IL-1β on Artn transcription.Conclusion IL-1β promotes Artn transcription in nucleus pulposus cells by up-regulating Runx1, induces the neuritogenesis and growth of neuronal neurites, and promotes the pathological nerve ingrowth into degenerated intervertebral discs. |
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