2. Academic Validation
  3. Screening chondrocyte necroptosis-related genes in the diagnosis and treatment of osteoarthritis

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

  • Heliyon. 2024 Jul 31;10(15):e35263. doi: 10.1016/j.heliyon.2024.e35263.
Muhai Deng 1,  Cong Tang 1,  Li Yin 2,  Junjun Yang 3,  Zhiyu Chen 4 5,  Yunsheng Jiang 1,  Yang Huang 6,  Cheng Chen 1
Affiliations

Affiliations

  • 1 College of Medical Informatics, Chongqing Medical University, Chongqing, 400016, China.
  • 2 Department of Orthopaedics, General Hospital of Western Theater Command, Chengdu, 610083, China.
  • 3 Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044, China.
  • 4 Orthopedic Laboratory of Chongqing Medical University, Chongqing, 400016, China.
  • 5 Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
  • 6 State Key Laboratory of Trauma, Burns and Combined Injury, Department of Wound Infection and Drug, Daping Hospital, Army Medical University, Chongqing, 400042, China.
PMID: 39170298 DOI: 10.1016/j.heliyon.2024.e35263
Abstract

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.

Keywords

Chondrocytes; Machine learning; Necroptosis; Osteoarthritis.

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