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| WANG Tianling,LV Qiao,ZHAI Yu.Research on the role and mechanism of glioma-associated oncogene homolog 1 in intervertebral disc degeneration[J].Chinese Journal of Spine and Spinal Cord,2025,(3):294-302. |
| Research on the role and mechanism of glioma-associated oncogene homolog 1 in intervertebral disc degeneration |
| Received:September 01, 2024 Revised:January 13, 2025 |
| English Keywords:Fibrosis Intervertebral disc degeneration Nucleus pulposus cell Glioma-associated oncogene homologous protein 1(Gli1) |
| Fund:国家自然科学基金面上项目（82172488）；陆军军医大学科技创新能力提升专项项目（2022XQN32） |
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| 【Abstract】 Objectives: To explore the impact of Gli1(gioma-associated oncogene homolog) on nucleus pulposus cells(NPCs) and its role in the fibrotic changes of the nucleus within intervertebral discs. Methods: A rat tail intervertebral disc puncture model was established. Histological staining was used to evaluate the levels of intervertebral disc degeneration and fibrotic changes in the untreated(negative control, NC) group and the puncture(puncture-induced intervertebral disc degeneration, PIDD) group. Western blot was used to assess the expression levels of Gli1 protein in the tissues. Gli1 protein was engineered to overexpress by lentivirus in NPCs and verified. The experiment was divided into three groups: control(Blank), Gli1 overexpression(Lv-Gli1), and virus control(lv-Ctrl). Immunofluorescence and Western blot were used to detect the expression levels of fibrotic markers FAP and FSP-1. Adding Gli1 inhibitor GANT61, cellular experiment was grouped into control(blank), Gli1 overexpression(Lv-Gli1), Gli1 overexpression+GANT61(Lv-Gli1+GANT61), and Gli1 overexpression+DMSO(Lv-Gli1+DMSO). Western blot was used to detect the expression levels of FAP and FSP-1 proteins. In vivo animal experiments were conducted in groups of puncture(PIDD), puncture treatment(PIDD+GANT61), and treatment control(PIDD+DMSO). Histological staining was used to evaluate the levels of intervertebral disc degeneration and fibrotic changes. Results: Histological staining results showed the histological score of degenerated discs significantly increased(P<0.01). Western blot results showed a significant increase in Gli1 protein expression in the degenerated group(P<0.05), which was consistent with the conclusions of the cellular experiments. NPCs overexpressing Gli1 protein were constructed, and immunofluorescence staining results showed that the expression of FAP and FSP-1 in the Gli1 overexpression group was significantly upregulated compared to the control and virus control groups. Western blot results further showed a significant increase in the expression of fibrotic markers in the Gli1 overexpression group(P<0.05). In the Gli1 overexpression+GANT61 group of the cellular experiment, compared to the control and Gli1 overexpression groups, Western blot indicated that the expressions of FAP and FSP-1 proteins were downregulated(P<0.05). In the in vivo experiment, the PIDD+GANT61 group showed a significant improvement in histological scores and collagen composition(P<0.05). Conclusions: The expression of Gli1 protein is significantly upregulated in degenerated nucleus pulposus tissue and NPCs; Inhibition of Gli1 gene expression downregulates the expressions of FAP and FSP-1 proteins. The mechanism of intervertebral disc fibrosis and degeneration may be associated with the activation of Gli1. |
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