TRIM29 alleviates intervertebral disc degeneration through the PI3K/AKT/mTOR pathway
Abstract Intervertebral disc degeneration (IDD), a prevalent spinal condition linked to low back pain, has substantial genetic components, necessitating deeper understanding of its mechanisms. This study categorized nucleus pulposus cell (NPC) populations and identified co-expression gene modules li...
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-10272-y |
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| author | Qinghua Yang Junfei Feng Hongyuan Xu Tao Kang Qingjun Wei Hua Jiang |
| author_facet | Qinghua Yang Junfei Feng Hongyuan Xu Tao Kang Qingjun Wei Hua Jiang |
| author_sort | Qinghua Yang |
| collection | DOAJ |
| description | Abstract Intervertebral disc degeneration (IDD), a prevalent spinal condition linked to low back pain, has substantial genetic components, necessitating deeper understanding of its mechanisms. This study categorized nucleus pulposus cell (NPC) populations and identified co-expression gene modules linked to the adhesive NPCs (Adh-NPCs) subpopulation in IDD using hierarchical dynamic weighted gene co-expression network analysis (hdWGCNA). Six key genes were distinguished through least absolute shrinkage and selection operator (LASSO) algorithms combined with machine learning approaches and receiver operating characteristic (ROC) curve analysis. Integrated analysis of RNA sequencing data, coupled with validation through polymerase chain reaction (PCR), western blot analysis, and immunohistochemistry in both clinical samples and IDD animal models, revealed a significant correlation between tripartite motif containing 29 (TRIM29) expression and IDD progression. Finally, functional experiments demonstrated that TRIM29 regulates intervertebral disc homeostasis and attenuates inflammatory responses in NPCs via the Phosphoinositide 3-Kinase (PI3K)/Protein Kinase B (AKT)/Mechanistic Target of Rapamycin (mTOR) pathway, suggesting its potential role in IDD prevention and treatment. In summary, our findings suggest that TRIM29 could play a modulatory role in IDD, potentially influencing disease progression through the PI3K/AKT/mTOR pathway. While further validation is needed, these observations may contribute to a deeper understanding of IDD pathogenesis. |
| format | Article |
| id | doaj-art-845d3c1c6d7e4f52be1960ded7fd70e6 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-845d3c1c6d7e4f52be1960ded7fd70e62025-08-20T03:04:34ZengNature PortfolioScientific Reports2045-23222025-07-0115111410.1038/s41598-025-10272-yTRIM29 alleviates intervertebral disc degeneration through the PI3K/AKT/mTOR pathwayQinghua Yang0Junfei Feng1Hongyuan Xu2Tao Kang3Qingjun Wei4Hua Jiang5Department of Spine Surgery, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Spine Surgery, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Spine Surgery, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Spine Surgery, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Orthopedic Surgery, The First Affiliated Hospital of Guangxi Medical UniversityDepartment of Spine Surgery, The First Affiliated Hospital of Guangxi Medical UniversityAbstract Intervertebral disc degeneration (IDD), a prevalent spinal condition linked to low back pain, has substantial genetic components, necessitating deeper understanding of its mechanisms. This study categorized nucleus pulposus cell (NPC) populations and identified co-expression gene modules linked to the adhesive NPCs (Adh-NPCs) subpopulation in IDD using hierarchical dynamic weighted gene co-expression network analysis (hdWGCNA). Six key genes were distinguished through least absolute shrinkage and selection operator (LASSO) algorithms combined with machine learning approaches and receiver operating characteristic (ROC) curve analysis. Integrated analysis of RNA sequencing data, coupled with validation through polymerase chain reaction (PCR), western blot analysis, and immunohistochemistry in both clinical samples and IDD animal models, revealed a significant correlation between tripartite motif containing 29 (TRIM29) expression and IDD progression. Finally, functional experiments demonstrated that TRIM29 regulates intervertebral disc homeostasis and attenuates inflammatory responses in NPCs via the Phosphoinositide 3-Kinase (PI3K)/Protein Kinase B (AKT)/Mechanistic Target of Rapamycin (mTOR) pathway, suggesting its potential role in IDD prevention and treatment. In summary, our findings suggest that TRIM29 could play a modulatory role in IDD, potentially influencing disease progression through the PI3K/AKT/mTOR pathway. While further validation is needed, these observations may contribute to a deeper understanding of IDD pathogenesis.https://doi.org/10.1038/s41598-025-10272-yIntervertebral disc degenerationTRIM29PI3K/AKT/mTOR pathwayNucleus pulposus |
| spellingShingle | Qinghua Yang Junfei Feng Hongyuan Xu Tao Kang Qingjun Wei Hua Jiang TRIM29 alleviates intervertebral disc degeneration through the PI3K/AKT/mTOR pathway Scientific Reports Intervertebral disc degeneration TRIM29 PI3K/AKT/mTOR pathway Nucleus pulposus |
| title | TRIM29 alleviates intervertebral disc degeneration through the PI3K/AKT/mTOR pathway |
| title_full | TRIM29 alleviates intervertebral disc degeneration through the PI3K/AKT/mTOR pathway |
| title_fullStr | TRIM29 alleviates intervertebral disc degeneration through the PI3K/AKT/mTOR pathway |
| title_full_unstemmed | TRIM29 alleviates intervertebral disc degeneration through the PI3K/AKT/mTOR pathway |
| title_short | TRIM29 alleviates intervertebral disc degeneration through the PI3K/AKT/mTOR pathway |
| title_sort | trim29 alleviates intervertebral disc degeneration through the pi3k akt mtor pathway |
| topic | Intervertebral disc degeneration TRIM29 PI3K/AKT/mTOR pathway Nucleus pulposus |
| url | https://doi.org/10.1038/s41598-025-10272-y |
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