Comprehensive Transcriptomic Analysis and Experimental Validation of Notochordal Cells and Nucleus Pulposus Cells: Uncovering Novel Therapeutic Targets for Intervertebral Disc Degeneration

作者：Yanhu Li, Peng Cheng, Haijun Zhang, Shijie Chen, Huan Liu, Kun Wang, Jing Wang, Xuewen Kang · 发表于：Current Issues in Molecular Biology · 年份：2025 · DOI：10.3390/cimb47121001 · 被引用次数：1 · 研究领域：Spine and Intervertebral Disc Pathology、Tendon Structure and Treatment、Scoliosis diagnosis and treatment

Current therapeutic strategies for intervertebral disc degeneration (IDD)-related low back pain are limited to symptomatic alleviation. Notochordal cells (NCs), as progenitor cells of the nucleus pulposus (NP), lead us to develop innovative NC-based new therapies for IDD. A total of 40 NP specimens, obtained according to IDD criteria with defined Pfirrmann grades and histological degeneration score, were categorized as either normal (Grade II) or degenerated (Grade IV). An IDD model was established in SD rats by needle puncture of the annulus fibrosus. Degenerated NP tissue was identified using MRI, H&E, Safranin O, and Masson staining. NCs and NP cells (NPCs) were isolated and identified based on specific cellular markers. Furthermore, mRNA-seq was performed to profile gene expression in these cells. GO annotation and KEGG pathway analysis were employed to perform functional enrichment analysis of the differentially expressed genes (DEGs). Cell viability was assessed using the CCK-8 assay. An in vitro cell degeneration model was established by treating NPCs with TBHP. Analysis of specific marker expression was performed using Western blotting, immunohistochemistry, and immunofluorescence. We found that the number of NCs in degenerated NP tissues was significantly reduced compared to those in normal NP tissues, but a small amount of notochordal cell markers could still be detected. Analysis of sequencing data identified 2391 upregulated and 3813 downregulated DEGs. GO enr...