Apoptosis Signal-Regulated Kinase-1 Promotes Nucleus Pulposus Cell Senescence and Apoptosis to Regulate Intervertebral Disc Degeneration.

Autor:	Zou M; Department of Spine Surgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China., Chen W; Department of Orthopedics, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China., Li J; Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China., Qi X; Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China., Wang X; Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China., Liu F; Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China., Hu J; Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China., Zhang Q; Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: qianshizhang@csu.edu.cn.
Jazyk:	angličtina
Zdroj:	The American journal of pathology [Am J Pathol] 2024 Sep; Vol. 194 (9), pp. 1737-1751. Date of Electronic Publication: 2024 Jun 13.
DOI:	10.1016/j.ajpath.2024.05.004
Abstrakt:	This study investigated the role of apoptosis signal-regulated kinase-1 (ASK1) in intervertebral disc degeneration (IDD). The nucleus pulposus (NP) tissues of non-IDD and IDD patients were subjected to hematoxylin and eosin, Safranin O-fast green, and immunohistochemical staining. Quantitative real-time PCR was used to assess the ASK1 mRNA level within NP tissue samples and cells. The Cell Counting Kit-8 assay, senescence-associated β-galactosidase staining, and flow cytometry were conducted to assess the viability, senescence, and apoptosis of NP cells, respectively. Extracellular matrix-related factors were detected using Western blot analysis. Furthermore, the effect of ASK1 on the IDD rat model was evaluated. Finally, c-Jun N-terminal kinase (JNK) inhibitors were used to verify the effect of the JNK/p38 signaling on IDD. ASK1 mRNA and protein were up-regulated within NP tissue samples from the IDD group, IL-1β-stimulated NP cells, and IDD rats. ASK1 inhibition promoted cell viability and repressed the senescence and apoptosis of NP cells, promoted collagen II and aggrecan, inhibited matrix metalloproteinase 3/9 and a disintegrin and metalloproteinase with thrombospondin motifs 4/5 protein levels, and increased NP cells in rat intervertebral disc tissues. ASK1 overexpression exerted the opposite effects of ASK1 inhibition on NP cells. Additionally, JNK/p38 signaling suppression could reverse the ASK1 up-regulation-induced dysfunction. In conclusion, ASK1 facilitated the senescence and apoptosis of NP cells in promoting IDD progression via the JNK/p38 pathway. Competing Interests: Disclosure Statement None declared. (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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