Abstract
Purpose :
This study aimed to suppress sclerostin/SOST expression under hyperglycemic conditions and evaluate its effect on inflammatory responses and microvascular complications.
Methods :
To ascertain the association between sclerostin expression and inflammatory cytokine release in retinal cells, we treated human retinal endothelial cells (HREC) with high glucose (HG) concentrations of 30 mM, and separately, with 50 ng of human vascular endothelial growth factor165 (VEGF). Hyperglycemic conditions were established, and SOST siRNA transfection was performed to knockdown sclerostin levels in HRECs.
Results :
The findings confirmed that hyperglycemia significantly amplified both sclerostin expression and inflammatory cytokine production. Following SOST siRNA treatment, we observed a substantial reduction in both sclerostin and inflammatory marker expression, achieved through the inhibition of the NF-κB pathway. Moreover, silencing of the Wnt antagonist sclerostin resulted in diminished angiogenic activity in HRECs, along with a decrease in the expression of vascular endothelial markers, as evidenced by a tube formation experiment.
In contrast, overexpression of sclerostin, achieved via clustered regularly interspaced short palindromic repeats (CRISPR)-SOST knockin, confirmed a surge in pro-inflammatory cytokine expression and enhanced tube formation capacity in HRECs.
Conclusions :
Our results establish a strong correlation between sclerostin and retinal vascular inflammation under hyperglycemic conditions, with a notable reduction in vascular inflammation following SOST inhibition. Therefore, we posit that SOST could be a potential therapeutic target for mitigating microvascular complications arising from diabetic retinopathy.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.