Single‐Cell Analysis Integrated With Machine Learning Elucidates the Mechanisms of Nucleus Pulposus Cells Apoptosis in Intervertebral Disc Degeneration and Therapeutic Interventions
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...
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Wiley
2025-03-01
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| Online Access: | https://doi.org/10.1002/jsp2.70036 |
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| author | Chao Song Xiaofei Wu Chaoqi Chen Baoxin Shen Yongliang Mei Qian Yan Feng Jiang Feng Chen Fei Liu |
| author_facet | Chao Song Xiaofei Wu Chaoqi Chen Baoxin Shen Yongliang Mei Qian Yan Feng Jiang Feng Chen Fei Liu |
| author_sort | Chao Song |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e503749265724985b799347b7a2ed910 |
| institution | Kabale University |
| issn | 2572-1143 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
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| series | JOR Spine |
| spelling | doaj-art-e503749265724985b799347b7a2ed9102025-08-20T03:48:45ZengWileyJOR Spine2572-11432025-03-0181n/an/a10.1002/jsp2.70036Single‐Cell Analysis Integrated With Machine Learning Elucidates the Mechanisms of Nucleus Pulposus Cells Apoptosis in Intervertebral Disc Degeneration and Therapeutic InterventionsChao Song0Xiaofei Wu1Chaoqi Chen2Baoxin Shen3Yongliang Mei4Qian Yan5Feng Jiang6Feng Chen7Fei Liu8Department of Orthopedics RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine Nanning ChinaDepartment of Orthopedics RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine Nanning ChinaDepartment of Orthopedics RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine Nanning ChinaDepartment of Orthopedics RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine Nanning ChinaDepartment of Orthopedics and Traumatology, the Affiliated Traditional Chinese Medicine Hospital Southwest Medical University Luzhou ChinaDepartment of Orthopedics RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine Nanning ChinaDepartment of Orthopedics and Traumatology, the Affiliated Traditional Chinese Medicine Hospital Southwest Medical University Luzhou ChinaDepartment of Orthopedics RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine Nanning ChinaDepartment of Orthopedics RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine Nanning ChinaABSTRACT 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.https://doi.org/10.1002/jsp2.70036apoptosisDuhuoimmune infiltrationintervertebral disc degenerationmacrophage |
| spellingShingle | Chao Song Xiaofei Wu Chaoqi Chen Baoxin Shen Yongliang Mei Qian Yan Feng Jiang Feng Chen Fei Liu Single‐Cell Analysis Integrated With Machine Learning Elucidates the Mechanisms of Nucleus Pulposus Cells Apoptosis in Intervertebral Disc Degeneration and Therapeutic Interventions JOR Spine apoptosis Duhuo immune infiltration intervertebral disc degeneration macrophage |
| title | Single‐Cell Analysis Integrated With Machine Learning Elucidates the Mechanisms of Nucleus Pulposus Cells Apoptosis in Intervertebral Disc Degeneration and Therapeutic Interventions |
| title_full | Single‐Cell Analysis Integrated With Machine Learning Elucidates the Mechanisms of Nucleus Pulposus Cells Apoptosis in Intervertebral Disc Degeneration and Therapeutic Interventions |
| title_fullStr | Single‐Cell Analysis Integrated With Machine Learning Elucidates the Mechanisms of Nucleus Pulposus Cells Apoptosis in Intervertebral Disc Degeneration and Therapeutic Interventions |
| title_full_unstemmed | Single‐Cell Analysis Integrated With Machine Learning Elucidates the Mechanisms of Nucleus Pulposus Cells Apoptosis in Intervertebral Disc Degeneration and Therapeutic Interventions |
| title_short | Single‐Cell Analysis Integrated With Machine Learning Elucidates the Mechanisms of Nucleus Pulposus Cells Apoptosis in Intervertebral Disc Degeneration and Therapeutic Interventions |
| title_sort | single cell analysis integrated with machine learning elucidates the mechanisms of nucleus pulposus cells apoptosis in intervertebral disc degeneration and therapeutic interventions |
| topic | apoptosis Duhuo immune infiltration intervertebral disc degeneration macrophage |
| url | https://doi.org/10.1002/jsp2.70036 |
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