Evidence map›Paper›PMID 39034400›Full record

ArticleJournal of orthopaedic surgery and research2024

The regulatory mechanism of cyclic GMP-AMP synthase on inflammatory senescence of nucleus pulposus cell.

Rui Sun, Feng Wang, Cong Zhong, Hang Shi, Xin Peng, Jia-Wei Gao, Xiao-Tao Wu

Abstract read
In one paragraph

Article in Journal of orthopaedic surgery and research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Rui SunDepartment of Orthopedics, School of Medicine, Zhongda Hospital, Southeast University, NO. 87 Ding Jia Qiao, Nanjing, Jiangsu Province, 210003, China.
Feng WangDepartment of Orthopedics, School of Medicine, Zhongda Hospital, Southeast University, NO. 87 Ding Jia Qiao, Nanjing, Jiangsu Province, 210003, China.
Cong ZhongDepartment of Orthopedics, School of Medicine, Zhongda Hospital, Southeast University, NO. 87 Ding Jia Qiao, Nanjing, Jiangsu Province, 210003, China.
Hang ShiDepartment of Orthopedics, School of Medicine, Zhongda Hospital, Southeast University, NO. 87 Ding Jia Qiao, Nanjing, Jiangsu Province, 210003, China.
Xin PengDepartment of Orthopedics, School of Medicine, Zhongda Hospital, Southeast University, NO. 87 Ding Jia Qiao, Nanjing, Jiangsu Province, 210003, China.
Jia-Wei GaoDepartment of Orthopedics, School of Medicine, Zhongda Hospital, Southeast University, NO. 87 Ding Jia Qiao, Nanjing, Jiangsu Province, 210003, China.
Xiao-Tao WuDepartment of Orthopedics, School of Medicine, Zhongda Hospital, Southeast University, NO. 87 Ding Jia Qiao, Nanjing, Jiangsu Province, 210003, China. wuxiaotaospine@seu.edu.cn.

Funding

National Natural Science Foundation of China 82202768National Natural Science Foundation of China 82372473Research Personnel Cultivation Programme of Zhongda Hospital Southeast University CZXM-GSP-RC52the Jiangsu Provincial medical Key Discipline (Laboratory) Cultivation Unit JSDW202222
6 · The paper itself

Abstract

backgroundCellular senescence features irreversible growth arrest and secretion of multiple proinflammatory cytokines. Cyclic GMP-AMP synthase (cGAS) detects DNA damage and activates the DNA-sensing pathway, resulting in the upregulation of inflammatory genes and induction of cellular senescence. This study aimed to investigate the effect of cGAS in regulating senescence of nucleus pulposus (NP) cells under inflammatory microenvironment.

methodsThe expression of cGAS was evaluated by immunohistochemical staining in rat intervertebral disc (IVD) degeneration model induced by annulus stabbing. NP cells were harvested from rat lumbar IVD and cultured with 10ng/ml IL-1β for 48 h to induce premature senescence. cGAS was silenced by cGAS specific siRNA in NP cells and cultured with IL-1β. Cellular senescence was evaluated by senescence-associated beta-galactosidase (SA-β-gal) staining and flow cytometry. The expression of senescence-associated secretory phenotype including IL-6, IL-8, and TNF-a was evaluated by ELISA and western blotting.

resultscGAS was detected in rat NP cells in cytoplasm and the expression was significantly increased in degenerated IVD. Culturing in 10ng/ml IL-1β for 48 h induced cellular senescence in NP cells with attenuation of G1-S phase transition. In senescent NP cells the expression of cGAS, p53, p16, NF-kB, IL-6, IL-8, TNF-α was significantly increased while aggrecan and collagen type II was reduced than in normal NP cells. In NP cells with silenced cGAS, the expression of p53, p16, NF-kB, IL-6, IL-8, and TNF-α was reduced in inflammatory culturing with IL-1β.

conclusioncGAS was increased by NP cells in degenerated IVD promoting cellular senescence and senescent inflammatory phenotypes. Targeting cGAS may alleviate IVD degeneration by reducing NP cell senescence.

Indexed as

Cellular SenescenceIntervertebral Disc DegenerationNucleotidyltransferasesNucleus PulposusRats, Sprague-DawleyAnimalsCells, CulturedInflammationInterleukin-1betaMaleRatsInterleukin-1betaNucleotidyltransferasescGASIL-1βIntervertebral disc degenerationNF-κB pathwayNucleus pulposus cellsSenescence

Identifiers

PMID39034400
PMCPMC11265083

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.