Serglycin secreted by late-stage nucleus pulposus cells is a biomarker of intervertebral disc degeneration
Abstract Intervertebral disc degeneration is a natural process during aging and a leading cause of lower back pain. Here, we generate a comprehensive atlas of nucleus pulposus cells using single-cell RNA-seq analysis of human nucleus pulposus tissues (three males and four females, age 41.14 ± 18.01...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-44313-9 |
| _version_ | 1797363151454339072 |
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| author | Fan Chen Linchuan Lei Shunlun Chen Zhuoyang Zhao Yuming Huang Guowei Jiang Xingyu Guo Zemin Li Zhaomin Zheng Jianru Wang |
| author_facet | Fan Chen Linchuan Lei Shunlun Chen Zhuoyang Zhao Yuming Huang Guowei Jiang Xingyu Guo Zemin Li Zhaomin Zheng Jianru Wang |
| author_sort | Fan Chen |
| collection | DOAJ |
| description | Abstract Intervertebral disc degeneration is a natural process during aging and a leading cause of lower back pain. Here, we generate a comprehensive atlas of nucleus pulposus cells using single-cell RNA-seq analysis of human nucleus pulposus tissues (three males and four females, age 41.14 ± 18.01 years). We identify fibrotic late-stage nucleus pulposus cells characterized by upregulation of serglycin expression which facilitate the local inflammatory response by promoting the infiltration of inflammatory cytokines and macrophages. Finally, we discover that daphnetin, a potential serglycin ligand, substantially mitigates the local inflammatory response by downregulating serglycin expression in an in vivo mouse model, thus alleviating intervertebral disc degeneration. Taken together, we identify late-stage nucleus pulposus cells and confirm the potential mechanism by which serglycin regulates intervertebral disc degeneration. Our findings indicate that serglycin is a latent biomarker of intervertebral disc degeneration and may contribute to development of diagnostic and therapeutic strategies. |
| first_indexed | 2024-03-08T16:17:30Z |
| format | Article |
| id | doaj.art-98595d5e2d6e47daae3501ea11b52c8a |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-08T16:17:30Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-98595d5e2d6e47daae3501ea11b52c8a2024-01-07T12:32:19ZengNature PortfolioNature Communications2041-17232024-01-0115111710.1038/s41467-023-44313-9Serglycin secreted by late-stage nucleus pulposus cells is a biomarker of intervertebral disc degenerationFan Chen0Linchuan Lei1Shunlun Chen2Zhuoyang Zhao3Yuming Huang4Guowei Jiang5Xingyu Guo6Zemin Li7Zhaomin Zheng8Jianru Wang9Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen UniversityDepartment of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen UniversityAbstract Intervertebral disc degeneration is a natural process during aging and a leading cause of lower back pain. Here, we generate a comprehensive atlas of nucleus pulposus cells using single-cell RNA-seq analysis of human nucleus pulposus tissues (three males and four females, age 41.14 ± 18.01 years). We identify fibrotic late-stage nucleus pulposus cells characterized by upregulation of serglycin expression which facilitate the local inflammatory response by promoting the infiltration of inflammatory cytokines and macrophages. Finally, we discover that daphnetin, a potential serglycin ligand, substantially mitigates the local inflammatory response by downregulating serglycin expression in an in vivo mouse model, thus alleviating intervertebral disc degeneration. Taken together, we identify late-stage nucleus pulposus cells and confirm the potential mechanism by which serglycin regulates intervertebral disc degeneration. Our findings indicate that serglycin is a latent biomarker of intervertebral disc degeneration and may contribute to development of diagnostic and therapeutic strategies.https://doi.org/10.1038/s41467-023-44313-9 |
| spellingShingle | Fan Chen Linchuan Lei Shunlun Chen Zhuoyang Zhao Yuming Huang Guowei Jiang Xingyu Guo Zemin Li Zhaomin Zheng Jianru Wang Serglycin secreted by late-stage nucleus pulposus cells is a biomarker of intervertebral disc degeneration Nature Communications |
| title | Serglycin secreted by late-stage nucleus pulposus cells is a biomarker of intervertebral disc degeneration |
| title_full | Serglycin secreted by late-stage nucleus pulposus cells is a biomarker of intervertebral disc degeneration |
| title_fullStr | Serglycin secreted by late-stage nucleus pulposus cells is a biomarker of intervertebral disc degeneration |
| title_full_unstemmed | Serglycin secreted by late-stage nucleus pulposus cells is a biomarker of intervertebral disc degeneration |
| title_short | Serglycin secreted by late-stage nucleus pulposus cells is a biomarker of intervertebral disc degeneration |
| title_sort | serglycin secreted by late stage nucleus pulposus cells is a biomarker of intervertebral disc degeneration |
| url | https://doi.org/10.1038/s41467-023-44313-9 |
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