Excessive accumulation of thioredoxin promotes osteogenic differentiation of mesenchymal stem cells of ligament in ankylosing spondylitis by upregulating autophagy levels.

BACKGROUND

Ankylosing spondylitis (AS) is an autoimmune disease characterized by dysfunction of the immune system, which leads to chronic inflammation and progressive ossification of spinal ligaments. The precise pathogenesis of this condition remains unclear, thereby impeding the development of effective treatments.

METHODS

We analyzed the GSE25101 dataset and identified the aberrant expression and potential pathogenic role of TXN. This was achieved through a combination of histopathological testing, quantitative PCR (qPCR), Western blotting (WB), and ELISA to elucidate its aberrant expression and distribution. The pathogenic role of TXN was further clarified by employing lentiviral infection, plasmid transfection, electron microscopy, ALP and ARS staining, WB, and qPCR. Finally, the osteogenic role of TXN in the ligaments of AS mice was further elucidated through in vivo plasmid transfection.

RESULTS

Through an analysis of the public database GSE25101, we identified abnormal transcription of thioredoxin (TXN) in peripheral blood mononuclear cells. Subsequent experiments utilizing ELISA, qPCR, immunohistochemistry, and immunofluorescence revealed a potential link between TXN expression and pathological ossification. KEGG and GO analyses, along with the application of lentivirus and plasmid treatments on mesenchymal stem cells (MSCs), indicated that TXN promotes the osteogenic differentiation of MSCs by activating their autophagy levels. Animal experiments further corroborated the role of TXN in facilitating pathological ossification of ligaments in mice.

CONCLUSIONS

Abnormal TXN expression in the immune system is closely associated with the development of pathological ossification in ankylosing spondylitis. Future research should aim to elucidate the underlying mechanisms, with the inhibition of TXN production emerging as a promising strategy for preventing spinal ligament ossification in this condition.