Abstract
AbstractIntervertebral 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.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Guangdong Province
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference54 articles.
1. Chou, R. Low back pain. Ann. Intern. Med. 174, ITC113–ITC128 (2021).
2. Knezevic, N. N., Candido, K. D., Vlaeyen, J. W. S., Van Zundert, J. & Cohen, S. P. Low back pain. Lancet 398, 78–92 (2021).
3. Risbud, M. V. & Shapiro, I. M. Role of cytokines in intervertebral disc degeneration: pain and disc content. Nat. Rev. Rheumatol. 10, 44–56 (2014).
4. Lyu, F. J. et al. Painful intervertebral disc degeneration and inflammation: from laboratory evidence to clinical interventions. Bone Res. 9, 7 (2021).
5. Roberts, S., Evans, H., Trivedi, J. & Menage, J. Histology and pathology of the human intervertebral disc. J. Bone Jt. Surg. Am. 88, 10–14 (2006).