Single‐Cell Analysis Integrated With Machine Learning Elucidates the Mechanisms of Nucleus Pulposus Cells Apoptosis in Intervertebral Disc Degeneration and Therapeutic Interventions

• Published in: JOR-spine Vol. 8; no. 1; pp. e70036 - n/a
• Main Authors: Song, Chao, Wu, Xiaofei, Chen, Chaoqi, Shen, Baoxin, Mei, Yongliang, Yan, Qian, Jiang, Feng, Chen, Feng, Liu, Fei
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.03.2025; Wiley
• Subjects: Algorithms; Apoptosis; Cells; Data processing; Degenerative disc disease; Duhuo; Gene expression; immune infiltration; Immunology; intervertebral disc degeneration; Machine learning; macrophage; Pharmacology; Software; Spine; Traditional Chinese medicine; intervertebral disc degeneration; apoptosis; macrophage; Duhuo; immune infiltration
• ISSN: 2572-1143; 2572-1143
• DOI: 10.1002/jsp2.70036

ABSTRACT Background The molecular of intervertebral disc degeneration (IVDD) is still unclear. When it comes to treating decoction, traditional Chinese medicine is effective. In particular, the Duhuo (Radix Angelicae Biseratae) may be particularly helpful. Purpose To identify nucleus pulposus cells (NPCs) subpopulations and immune cells and clarify the mechanism of IVDD therapy, offering recommendations for diagnosis and treatment. Methods IVDD targets from the Genecards and microarray data from biological databases. To find the key genes and biological pathways underlying IVDD, multiple machine learning techniques were used. IVDD is associated with subpopulations of NPCs as revealed by single‐cell analysis, and immunological infiltration was identified by Immune Cell AI. To validate the molecular pathways by which Duhuo activity affects IVDD, network pharmacology and molecular docking were employed. Results The process of IVDD is linked to key genes like TP53, JUN, PTEN, IL1B, ERBB2, MAPK8, CASP9, PTK2, etc. The main molecular mechanisms involved in this process are immune responses, inflammatory factors expression, cellular responses to mechanical stimuli, and NPC apoptosis. Immune Cell AI discovered a correlation between CD4 naïve, B cell, monocyte, NK, and macrophage infiltration with the development of IVDD. The NPC subtypes associated with IVDD, namely fibroNPCs, adhesion NPCs, regulatory NPCs, homeostatic NPCs, and hypertrophic chondrocyte‐like NPCs (HT‐CL NPCs), were the subject of single‐cell mapping. We also found that Osthole, Columbianadin, and Bergapten, the principal blood entry components of Dohuo, may have a role by modulating CASP9, MAPK8, PTGS1, and PARP1, the targets of apoptosis. Conclusion The NPC subpopulations that exist in IVDD are HT‐CL NPCs, fibroNPCs, adhesion NPCs, regulatory NPCs, and homeostatic NPCs. Furthermore, a variety of immune cell infiltrates, particularly monocyte and macrophage, have a significant impact on the advancement of IVDD. Osthole, Columbianadin, and Bergapten, the principal components of Duhuo, absorb IVDD via controlling the death of NPCs. IVDD has various NPC subgroups, including HT‐CLNP, fibrous NPC, sticky NPC, regulatory NPC, and steady‐state NPC. Furthermore, numerous immune cell infiltrates, particularly monocytes and macrophages, play a crucial role in the evolution of IVDD. Parthenogenesis' key components are Osthole, Columbianadin, and Bergapten, which absorb IVDD by managing NPCs death.