Analysis of Molecular Changes and Features in Rat Knee Osteoarthritis Cartilage: Progress From Cellular Changes to Structural Damage

Author:

Zhao Zixi1ORCID,Ito Akira1ORCID,Kuroki Hiroshi1,Aoyama Tomoki1

Affiliation:

1. Department of Motor Function Analysis, Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan

Abstract

Objective Although knee osteoarthritis (KOA) is a common disease, there is a lack of specific prevention and early treatment methods. Hence, this study aimed to examine the molecular changes occurring at different stages of KOA to elucidate the dynamic nature of the disease. Design Using a low-force compression model and analyzing RNA sequencing data, we identified molecular changes in the transcriptome of knee joint cartilage, including gene expression and molecular pathways, between the cellular changes and structural damage stages of KOA progression. In addition, we validated hub genes using an external dataset. Results Gene set enrichment analysis (GSEA) identified the following pathways to be associated with KOA: “B-cell receptor signaling pathway,” “cytokine-cytokine receptor interaction,” and “hematopoietic cell lineage.” Expression analysis revealed 585 differentially expressed genes, with 579 downregulated and 6 upregulated genes. Enrichment and clustering analyses revealed that the main molecular clusters were involved in cell cycle regulation and immune responses. Furthermore, the hub genes Csf1r, Cxcr4, Cxcl12, and Ptprc were related to immune responses. Conclusions Our study provides insights into the dynamic nature of early-stage KOA and offers valuable information to support the development of effective intervention strategies to prevent the irreversible damage associated with KOA, thereby addressing a major clinical challenge.

Funder

Japan Society for the Promotion of Science

Japan Science and Technology Agency

Publisher

SAGE Publications

Subject

Physical Therapy, Sports Therapy and Rehabilitation,Biomedical Engineering,Immunology and Allergy

Reference48 articles.

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