Screening chondrocyte necroptosis-related genes in the diagnosis and treatment of osteoarthritis

作者全名："Deng, Muhai; Tang, Cong; Yin, Li; Yang, Junjun; Chen, Zhiyu; Jiang, Yunsheng; Huang, Yang; Chen, Cheng"

作者地址："[Deng, Muhai; Tang, Cong; Jiang, Yunsheng; Chen, Cheng] Chongqing Med Univ, Coll Med Informat, Chongqing 400016, Peoples R China; [Yin, Li] Gen Hosp Western Theater Command, Dept Orthopaed, Chengdu 610083, Peoples R China; [Yang, Junjun] Chongqing Univ, Coll Bioengn, Key Lab Biorheol Sci & Technol, Minist Educ, Chongqing 400044, Peoples R China; [Chen, Zhiyu] Chongqing Med Univ, Orthoped Lab, Chongqing 400016, Peoples R China; [Chen, Zhiyu] Chongqing Med Univ, Affiliated Hosp 1, Dept Orthoped, Chongqing 400016, Peoples R China; [Huang, Yang] Army Med Univ, Daping Hosp, Dept Wound Infect & Drug, State Key Lab Trauma Burns & Combined Injury, Chongqing 400042, Peoples R China"

通信作者："Chen, C (通讯作者)，Chongqing Med Univ, Coll Med Informat, Chongqing 400016, Peoples R China.; Huang, Y (通讯作者)，Army Med Univ, Daping Hosp, Dept Wound Infect & Drug, State Key Lab Trauma Burns & Combined Injury, Chongqing 400042, Peoples R China."

来源：HELIYON

ESI学科分类：　

WOS号：WOS:001287604900001

JCR分区：Q2

影响因子：4

年份：2024

卷号：10

期号：15

开始页：　

结束页：　

文献类型：Article

关键词：Osteoarthritis; Chondrocytes; Necroptosis; Machine learning

摘要："Background: Osteoarthritis (OA) is the most common form of joint diseases, with hallmark of cartilage degeneration. Recent studies have shown that the pathogenesis of OA is associated with chondrocyte necroptosis. Methods: In this study, we used single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data to analyze necroptosis regulation in OA chondrocytes. We performed enrichment analysis, carried out experimental validation, constructed machine learning models, and docked drug molecules. Results: After least absolute shrinkage and selection operator (LASSO) algorithm screening, 4 hub genes (RIPK3, CYBB, HSP90AB1, and TRAF5) with diagnostic characteristics were obtained. Following the comparison of multiple models, the Bayesian model with an average area under curve (AUC) value of 0.944 was finally selected. We found that nimesulide exhibited strong binding affinity to CYBB and HSP90AB1, and experimentally verified that nimesulide reduced the expression of RIPK3 and CYBB, suggesting its potential as an inhibitor of chondrocyte necroptosis. Furthermore, scRNA-seq results showed that necroptosis in OA was significantly upregulated on regulatory chondrocytes (RegC) compared to other chondrocyte subtypes. Conclusions: The results indicate that nimesulide might be used to treat OA by inhibiting chondrocyte necroptosis through down-regulation of RIK3 and CYBB genes. This study reveals the role of chondrocyte necroptosis in OA, and suggests a potential therapeutic strategy by regulating necroptosis with nimesulide."

基金机构：Postdoctoral Research Project of Chongqing [2021XM3092]; Natural Science Foundation of Chongqing [cstb2022nscq-msx0139]; Future Medical Innovation Team of Chongqing Medical University [W0080]

基金资助正文："<BOLD>Acknowledgements</BOLD> This study was supported by Postdoctoral Research Project of Chongqing (2021XM3092) , the Natural Science Foundation of Chongqing (cstb2022nscq-msx0139) , and the Future Medical Innovation Team of Chongqing Medical University (W0080) ."