Thiotaurine and sulfane sulfur signaling: a redox-based strategy against osteoarthritis inflammation

Hydrogen sulfide (H2S) has emerged as a key gasotransmitter involved in the regulation of inflammation, oxidative stress response, and cellular signaling. In osteoarthritis, a prevalent and disabling joint disease characterized by chronic inflammation and cartilage degradation, H2S has demonstrated promising therapeutic effects. Thiotaurine (2-aminoethane thiosulfonate) is a naturally occurring sulfur-containing compound characterized by the presence of a thiosulfonate group, in which one sulfur atom is bound to another, often referred to as “sulfane sulfur.” The sulfur–sulfur bond in thiosulfonates is readily cleaved by thiol compounds and reducing agents, forming persulfides or undergoing reduction to H2S. Thiotaurine thus acts as a biologically relevant H2S donor through thiol-dependent persulfidation, a post-translational modification implicated in redox signaling. This study aimed to evaluate the anti-inflammatory potential of thiotaurine in human primary chondrocytes under pro-inflammatory stimulation. Cell viability assays confirmed no cytotoxicity at concentrations up to 1 mM thiotaurine. Pre-treatment with thiotaurine (50-100 μM) significantly reduced TNF-α-induced mRNA and protein levels of IL-6, IL-8, and IL-1β. Furthermore, immunofluorescence analysis revealed that thiotaurine inhibited p65 phosphorylation and nuclear translocation, key steps in NF-κB pathway activation. Persulfide detection assays confirmed enhanced intracellular persulfide formation in thiotaurine-treated cells. These findings suggest that thiotaurine exerts its effects through NF-κB inhibition and promotion of persulfidation, leading to decreased inflammatory mediator production. Given its endogenous origin, favorable safety profile, and dual role in H2S release and redox modulation, thiotaurine represents a promising candidate for therapeutic application in osteoarthritis and potentially other inflammatory conditions.