Serglycin secreted by late-stage nucleus pulposus cells is a biomarker of intervertebral disc degeneration

Fan Chen, Linchuan Lei, Shunlun Chen, Zhuoyang Zhao, Yuming Huang, Guowei Jiang, Xingyu Guo, Zemin Li, Zhaomin Zheng () and Jianru Wang ()
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Fan Chen: The First Affiliated Hospital of Sun Yat-sen University
Linchuan Lei: The First Affiliated Hospital of Sun Yat-sen University
Shunlun Chen: The First Affiliated Hospital of Sun Yat-sen University
Zhuoyang Zhao: The First Affiliated Hospital of Sun Yat-sen University
Yuming Huang: The First Affiliated Hospital of Sun Yat-sen University
Guowei Jiang: The First Affiliated Hospital of Sun Yat-sen University
Xingyu Guo: The First Affiliated Hospital of Sun Yat-sen University
Zemin Li: The First Affiliated Hospital of Sun Yat-sen University
Zhaomin Zheng: The First Affiliated Hospital of Sun Yat-sen University
Jianru Wang: The First Affiliated Hospital of Sun Yat-sen University

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-023-44313-9

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