Thiotaurine as a Sulfane Sulfur Intermediate in Hydrogen Sulfide Signaling: Regulation of Persulfidation and NF-κAPPA B Pathway in Human Chondrocytes

Hydrogen sulfide (H2S) is an endogenous gasotransmitter involved in the regulation of inflammation, redox homeostasis, and cartilage metabolism. Reduced H2S bioavailability has been associated with osteoarthritis, suggesting that restoration of sulfide signaling may represent a promising therapeutic strategy. Within the reactive sulfur species (RSS) network, sulfane sulfur–containing metabolites act as dynamic reservoirs controlling sulfide availability and protein persulfidation. Among these intermediates, thiotaurine (2-aminoethane thiosulfonate) has recently emerged as a physiologically relevant sulfane sulfur compound capable of acting as a storage and donor form of H2S [1]. In this study, we investigated the role of thiotaurine as a biologically active sulfane sulfur donor regulating redox-sensitive inflammatory signaling in primary human chondrocytes exposed to TNF-α stimulation. Thiotaurine showed no cytotoxic effects at concentrations up to 1 mM and significantly reduced TNF-α–induced expression and secretion of IL-6, IL-8, and IL-1β at micromolar concentrations. Mechanistically, thiotaurine markedly inhibited phosphorylation and nuclear translocation of the NF-κB p65 subunit, indicating suppression of a key transcriptional regulator of inflammatory responses. Fluorescence-based assays demonstrated increased intracellular persulfide formation following thiotaurine treatment, supporting its function as an efficient sulfane sulfur donor capable of modulating the cellular persulfidation landscape. These findings identify thiotaurine as an important intermediate within the H2S/RSS signaling axis and support its potential therapeutic relevance in inflammation-driven diseases such as osteoarthritis. The health benefits of sulfur-based therapy, such as sulfur water springs, garlic, and cruciferous vegetables, have been recognized since ancient times. Notably, the common denominator in these remedies lies in their ability to supply H2S/sulfane sulfur.