Decreased FoxO1 expression contributes to facet joint osteoarthritis pathogenesis by impairing chondrocyte migration and extracellular matrix synthesis

Facet joint osteoarthritis (FJOA), a condition commonly observed in individuals of middle to old age, has been relatively under-researched compared to other subtypes of osteoarthritis (OA). This study investigated the role of transcription factor FoxO1 in FJOA using a Col2a1-creERT knock-in mouse model. It was found that FoxO1 deletion led to severe osteoarthritic changes, indicating that FoxO1 played a critical role in cartilage homeostasis. Transcriptome sequencing was performed on degenerated cartilage from FoxO1-deleted mice. This process identified differentially expressed genes (DEGs), offering insights into the molecular mechanisms underlying FJOA. Bioinformatics analysis, including Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrich-ment Analysis (GSEA) and protein-protein interaction (PPI) network analysis, identified Itgb3, Itga1, Itga6, Itga7, Itga8, Itga10, Col1a1, and Il6, as potential key contributors to FJOA after FoxO1 deletion. Importantly, over -expression of Itgb3 and inhibition of Il6 counteracted FoxO1 knockdown-induced impairments in chondrocyte migration and extracellular matrix synthesis, respectively. This study discovered FoxO1 as a key regulator of the pathogenesis of FJOA, helped unravel the complex molecular mechanisms underlying FJOA, and contributed to the development of promising therapeutic avenues toward FJOA.

Automated summary

This study investigated the role of transcription factor FoxO1 in facet joint osteoarthritis (FJOA) and found that FoxO1 deletion led to severe osteoarthritic changes. Transcriptome sequencing and bioinformatics analysis identified differentially expressed genes (DEGs) and potential key contributors to FJOA. Additionally, over-expression of certain genes and inhibition of others were shown to counteract the impairments caused by FoxO1 deletion in chondrocyte migration and extracellular matrix synthesis. These findings help unravel the molecular mechanisms underlying FJOA and open up promising therapeutic avenues for its treatment.