2025: Quercetin Simultaneously Treats Skeletal Fluorosis and KBD by Modulating HIF-1 and Ferroptosis Signaling Pathways

pfpcnews · Post by **pfpcnews** » Sat Apr 05, 2025 6:29 pm

Liu B, Wang Y, Zhu J, Huang H, Chen R, Yu F, Zhou G, Ba Y - "Quercetin Simultaneously Treats Skeletal Fluorosis and Kashin-Beck Disease by Modulating HIF-1 and Ferroptosis Signaling Pathways" Biol Trace Elem Res (2025 Apr 4) doi: 10.1007/s12011-025-04604-2
https://link.springer.com/article/10.10 ... 25-04604-2

Abstract

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.

NOTE: Kashin-Beck disease (KBD) is an endemic osteoarthropathy prevalent in certain regions of China. It primarily affects children and is linked to selenium deficiency, although high fluoride exposure has also been implicated in its etiology.

The co-occurrence of fluorosis and KBD in several Chinese regions is well-documented. Some researchers have proposed that fluoride may exacerbate KBD symptoms, particularly in the context of low selenium status.

Since fluoride interferes with deiodinases - which depend on selenium as a cofactor - an interaction between the two is not only plausible, but likely.

"D3 expression is induced by hypoxia-inducible factor 1α (HIF-1a), dampening T3 signaling and the metabolic rate. The coordinated expression of these enzymes adjusts TH signaling in a time- and tissue-specific fashion, affecting metabolic pathways in health and disease states." (Russo et al., 2021).

Both fluoride and excess iodine may act as triggers for the hypoxia signaling pathway, altering thyroid hormone metabolism and contributing to the shared pathology observed in skeletal fluorosis and KBD.

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