Males and Females Have Distinct Molecular Events in the Articular Cartilage during Knee Osteoarthritis

Osteoarthritis (OA) is a major public health challenge that imposes a remarkable burden on the affected individuals and the healthcare system. Based on the clinical observation, males and females have different prevalence rates and severity levels of OA. Thus, sex-based differences may play essential roles in OA's prognosis and treatment outcomes. To date, the comprehensive understanding of the relationship between sex and OA is still largely lacking. In the current study, we analyzed a published transcriptome dataset of knee articular cartilage (GSE114007) from 18 healthy (five females, 13 males) and 20 OA (11 females, nine males) donors to provide a slight insight into this important but complex issue. First, comparing female healthy cartilage samples with those of males revealed 36 differential expression genes (DEGs), indicating the fundamental sex-related differences at the molecular level. Meanwhile, 923 DEGs were distinguished between OA and healthy female cartilage, which can be enriched to 15 Reactome pathways. On the other hand, when comparing OA and healthy male cartilage, there are only 419 DEGs were identified, and only six pathways were enriched against the Reactome database. The different signaling response to OA in the male and female cartilage was further enforced by recognizing 50 genes with significantly different OA-responsive expression fold changes in males and females. Particularly, 14 Reactome pathways, such as Extracellular matrix organization, Collagen biosynthesis and modifying enzymes, Dissolution of fibrin clot, and Platelet Aggregation (Plug formation), can be noted from these 50 sex-dependent OA-responsive genes. Overall, the current study explores the Sex as a Biological Variable (SABV) at the transcriptomic level in the knee articular cartilage in both healthy status and OA event, which could help predict the differential OA prognosis and treatment outcome of males and female patients.

Automated summary

There are significant differences at the transcriptomic level in knee articular cartilage among healthy and OA individuals, particularly with regards to sex distinctions. Females showed more differential gene expression and enriched pathways in comparison to males, both in healthy cartilage and in OA conditions. Male and female cartilage responded differently to OA, with notable differences in the expression of genes related to various pathways, suggesting potential implications for OA prognosis and treatment outcomes in males and females.