What question did this study set out to answer?

This study aims to evaluate the impact of sulfate-arsenical-ferruginous water on apoptosis and gene expression in osteoarthritic chondrocytes stimulated by interleukin-1β.

April 24, 2026Open Access

A sulfate-arsenical-ferruginous water affects apoptosis, oxidative stress and the gene expression of inflammatory mediators and of a panel of MicroRNA in IL-1β stimulated human osteoarthritic chondrocytes

AFAntonella Fioravanti PMPatrizia ManicaLeco Corporation (United States)ISIole SeccaficoAzienda Ospedaliera Universitaria Senese

Key Points

This study aims to evaluate the impact of sulfate-arsenical-ferruginous water on apoptosis and gene expression in osteoarthritic chondrocytes stimulated by interleukin-1β.
Chondrocytes were isolated from osteoarthritis patients and treated with sulfate-arsenical-ferruginous water and interleukin-1β for 24 and 48 hours.
Apoptosis and oxidative stress were measured using cytometry, and gene expression levels were analyzed with Quantitative Real-Time PCR.
The role of NF-κB signaling was investigated with a specific inhibitor during treatment.
Sulfate-arsenical-ferruginous water enhanced cell viability and reduced apoptosis and oxidative stress at 25% and 50% concentrations.
At 50% concentration, LW significantly inhibited the expression of pro-inflammatory cytokines and metalloproteinases while enhancing certain microRNA levels.
Pre-treatment with a specific NF-κB inhibitor augmented the protective effects of LW against IL-1β-induced damage.

Abstract

Background The beneficial effects of balneotherapy in osteoarthritis (OA) using the sulfate-arsenicalferruginous Levico water (LW) have been recognized by several clinical studies. However, the specific biological properties of LW are partially understood. Objective The present study aimed at evaluating the ability of LW in the regulation of apoptosis, oxidative stress and of the gene expression of a panel of articular cartilage markers and MicroRNA ( miRNA ) in human osteoarthritic chondrocytes exposed to interleukin ( IL )- 1 β. Methods Chondrocytes were obtained from the femoral heads of patients with OA who underwent surgery for total hip prostheses. The cells were incubated for 24 h and 48 h with different concentrations of LW, alone or in combination with IL-1 β (10 ng/ml). Apoptosis and mitochondrial superoxide anion production were detected by cytometry. Gene levels of antioxidant enzymes, B-cell lymphoma ( BCL)2 , cytokines IL-1 β , IL-6 , tumor necrosis factor ( TNF )-α, metalloproteinases ( MMPs )1 and 13, type II collagen ( Col2a1 ), aggrecan , and of a pattern of miRNA were evaluated by Quantitative Real-Time PCR analysis (PCR). The involvement of nuclear factor ( NF ) - κ B was investigated by PCR and immunofluorescence and by pre-incubation with a specific inhibitor ( BAY 117082, IKK α / β). Results LW at 50% or 25% concentration counteracted the negative effects of IL-1 β on cell viability, apoptosis and mitochondrial superoxide anion production and on the gene expression of antioxidant enzymes, in a dose-dependent manner. The treatment of chondrocytes with 50% of LW significantly inhibited the gene expression of pro-inflammatory cytokines, MMPs and of miR-34a and miR-181a , while it upregulated miR-140 in IL-1 β stimulated cells. The pre-incubation with BAY 11–7082, IKK α / β reduced the damage induced by IL-1 β, and, interestingly, potentiated the properties of LW. Conclusions Our data demonstrated the ability of LW to regulate apoptosis, oxidative stress and gene expression of main factors implicated in OA pathogenesis through a possible modulation of NF- κ B signaling pathway. This study supports the use of balneotherapy with a sulfate-arsenical-ferruginous mineral water in the treatment of OA.

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