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ORIGINAL RESEARCH ARTICLE

Identification and immunological characteristics of autophagy and apoptosis genes in knee osteoarthritis: A bioinformatics analysis 

Xiaofeng Li1 ,  YuMing Li1 ,  Junfu Na2 ,  Yuanlu Liu2 ,  Yipin Wang2*
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1 Department of Orthopedics II, Dalian Jinzhou District Traditional Chinese Medicine Hospital, Dalian, Liaoning, China
2 Department of Orthopedics I, the First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China
OTE, 025470020 https://doi.org/10.36922/OTE025470020
Received: 18 November 2025 | Revised: 18 December 2025 | Accepted: 28 January 2026 | Published online: 22 April 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Knee osteoarthritis (KOA) is a degenerative joint disease characterized by cartilage degradation, synovial inflammation, and subchondral bone remodeling. The interplay between autophagy and apoptosis plays a critical role in chondrocyte homeostasis and disease progression. However, the shared molecular mechanisms linking these two processes to KOA pathogenesis remain incompletely understood. This study aims to identify key autophagy- and apoptosis-related genes and investigate their immunological characteristics in KOA. This study examines KOA to identify key genes associated with whole-joint components and analyze the relationship and underlying mechanisms between autophagy and apoptosis. Data from the GSE169077 dataset were extracted from the Gene Expression Omnibus database, and differential gene expression was analyzed using the edgeR model. Autophagy- and apoptosis-related genes were screened using the GeneCards database, and a protein–protein interaction network was constructed for functional pathway enrichment analysis. Further immune cell infiltration analysis was conducted, and machine learning algorithms were employed to identify two characteristic genes, SPARC and BNIP3. The results revealed 641 downregulated genes and 722 upregulated genes in KOA, with 73 overlapping genes linked to the phosphoinositide 3-kinase/protein kinase B, p53, and hypoxia-inducible factor 1 signaling pathways, and significant differences in macrophages. SPARC and BNIP3 influence the progression of KOA through mechanisms such as hypoxic response, cell membrane permeability, mitochondrial dysfunction, and vascular development. The study suggests that SPARC and BNIP3 could be potential targets involved in the association between KOA and both autophagy and apoptosis.

Keywords
Knee osteoarthritis
Differentially expressed genes
Machine learning
Bioinformatics
Immune infiltration
Funding
This study was supported by the Liaoning Provincial Administration of Traditional Chinese Medicine Project (Grant No. 2022-01) and the Shenyang Science and Technology Bureau Fund (Grant No. 22-321-34-10).
Conflict of interest
The authors declare they have no competing interests.
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