Quercetin Simultaneously Treats Skeletal Fluorosis and Kashin-Beck Disease by Modulating HIF-1 and Ferroptosis Signaling Pathways.

Excessive fluoride exposure can lead to skeletal fluorosis (SF), and selenium deficiency is one of the important pathogenic factors of Kashin-Beck disease (KBD). Although the pathogenic factors of these two diseases vary, there are many similarities in their pathogenic mechanisms on skeletal and articular cartilage lesions. There are currently no specific drugs for either disease, and investigating their shared pathogenic mechanisms may facilitate the development of new drugs for the treatment. This study found through bioinformatics technology that the HIF-1 signaling pathway and ferroptosis pathway might exert significant effects in both SF and KBD. Targeted small molecule drug prediction was conducted for the above two signaling pathways, and quercetin was screened as the best candidate therapeutic drug. Meanwhile, molecular docking and molecular dynamics simulations once again validated our screening results. In summary, quercetin may alleviate the symptoms of SF and KBD by regulating the HIF-1 signaling pathway and the ferroptosis pathway. In other words, it can attain the objective of treating two diseases simultaneously with one drug. This will provide new theoretical references for the treatment of comorbidity.