Comprehensive Analysis Reveals the Potential Diagnostic Value of Biomarkers Associated With Aging and Circadian Rhythm in Knee Osteoarthritis

Orthopaedic Surgery, 2025 · DOI: https://doi.org/10.1111/os.14370 · Published: January 12, 2025

Simple Explanation

This study investigates the relationship between aging, circadian rhythms, and knee osteoarthritis (KOA). It aims to identify genes linked to both aging and circadian rhythms that are differentially expressed in KOA patients compared to healthy individuals. The researchers used Mendelian randomization to explore causal relationships between these genes and KOA, followed by functional enrichment and immune infiltration analyses to understand the underlying mechanisms. They further validated their findings using human cartilage tissue and cell models. The study identified two potential biomarkers, PFKFB4 and DDIT4, associated with aging-circadian rhythm in KOA, offering new perspectives for disease prevention and treatment. These biomarkers showed significant differences in expression between normal and KOA tissues and affected cell proliferation and migration in lab experiments.

Study Duration

Not specified

Participants

KOA and normal samples from the GEO database, 403,124 samples for KOA GWAS

Evidence Level

Level 3, Mendelian Randomization, In vitro experiments

Key Findings

1
Identified 75 differentially expressed aging-circadian rhythm related genes between normal and KOA groups, primarily enriched in the circadian rhythm pathway.
2
Screened two biomarkers (PFKFB4 and DDIT4) by Mendelian Randomization analysis, suggesting their potential as diagnostic and therapeutic targets.
3
Immune infiltration analysis showed significant differences in three types of immune cells (resting dendritic cells, resting mast cells, and M2 macrophages) between the normal and KOA groups.

Research Summary

This study aimed to explore the role of aging and circadian rhythm-related genes in knee osteoarthritis (KOA). Differentially expressed genes (DEGs) were identified from the GEO database and intersected with aging-related circadian rhythm genes. Mendelian randomization (MR) analysis was conducted to investigate the causal relationship between these genes and KOA. Functional analysis, molecular mechanism exploration, and experimental validation further elucidated their roles in KOA. The study identified DDIT4 and PFKBF4 as potential diagnostic and therapeutic biomarkers associated with aging and circadian rhythms in KOA, offering new insights for the prevention and treatment of the disease.

Practical Implications

Diagnostic Biomarkers

PFKFB4 and DDIT4 can serve as potential biomarkers for the early diagnosis of KOA, allowing for timely intervention.

Therapeutic Targets

Targeting PFKFB4 and DDIT4 may provide novel therapeutic strategies for the treatment of KOA, potentially slowing down or reversing disease progression.

Personalized Medicine

Understanding the relationship between aging-circadian rhythms and KOA can contribute to personalized treatment approaches based on individual genetic and lifestyle factors.

Study Limitations

1
The expression levels of biomarkers were assessed in a small number of clinical samples.
2
The underlying mechanisms of the functional roles of biomarkers at the cellular level require further targeted basic research.
3
Further studies should focus on increasing the sample size to further validate the accuracy of these findings.

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