Table 2.
In vitro studies on human and animal samples evaluating the beneficial effects of BT on joint disorders
| Authors | Treatment(s) | Experimental model | Mineral water or inorganic or organic components | Pathology | Biochemical parameters | Results |
|---|---|---|---|---|---|---|
| (Kloesch et al. 2010) |
NaHS (0.030–1.0 mM) dissolved in the culture medium, for 1, 3, 6, 12 h + IL-1β (5 ng/mL) for 1 h |
RA human fibroblast-like synoviocytes | NaHS | Rheumatoid Arthritis |
IL-6; P38/MAPK/ERK signaling activation/deactivation |
Reduced IL-6 expression and activation of MAPK/ERK signaling (low NaHS concentrations) Increased IL-6 expression and activation of MAPK/ERK signaling (high NaHS concentrations) Reduction of inflammatory events of RA |
| (Kloesch et al. 2011) | NaHS (1.0 mM) dissolved in the culture medium, for 1, 3, 6, 12 h | RA and OA human fibroblast-like synoviocytes | NaHS | Rheumatoid Arthritis and Osteoarthritis |
IL-6, IL-8, COX-2; MMP-2, MMP-3, MMP-14; P38/MAPK/ERK protein expression |
Increased IL-6, IL-8, COX-2 and p38/MAPK/ERK expression Increase of inflammatory events of RA and OA |
| (Kloesch et al. 2012a; Kloesch et al. 2012b) |
NaHS (0.125 and 1.0 mM) dissolved in the culture medium, for 15, 30, 45 and 60 min + MAPK inhibitors (1 and 5 μM) + IL-1β (5 ng/mL) for 1 h |
Human chondrocyte cell line (C-28/I2) | NaHS | Rheumatoid Arthritis |
IL-6, IL-8; P38/MAPK/ERK and NF-kB signaling activation/deactivation |
Reduced IL-6 and IL-8 expression and activation of p38/MAPK/ERK and NF-kB signaling Reduction of inflammatory processes of arthritis |
| (Fox et al. 2012) |
IL-1β, IL-6 and TNF-α (5 ng/mL) for 6, 12 and 18 h + GYY4137 (50–500 mol/L) dissolved in the culture medium, for 12 h |
Human primary articular chondrocytes | GYY4137 | Rheumatoid Arthritis |
Cell death; Mitochondrial membrane potential |
Reduced cell death and oxidant-induced mitochondrial dysfunction Limitation of inflammation in chronic inflammatory diseases |
| (Li et al. 2013) |
GYY4137 (0.1–0.5 mM) dissolved in the culture medium, for 18 h + LPS (10 μg/mL) |
Human primary arthritis synoviocytes and chondrocytes | GYY4137 | Rheumatoid arthritis |
IL-6, TNF-α, PGE2, COX-2; NO, iNOS; NF-kB signaling activation/deactivation |
Reduced IL-6, TNF-α, PGE2 and NO production, COX-2 and iNOS catalytic activity, and NF-kB activation Reduction of inflammatory processes of arthritis |
| (Burguera et al. 2014) |
NaHS and GYY4137 (0.05–1 mM) dissolved in the culture medium, for 24 or 48 h + IL-1β (5 ng/mL) |
Human primary OA chondrocytes | NaHS and GYY4137 | Osteoarthritis |
IL-6, PGE2, PTGES, COX-2; NO, NOS2; MMP-13; NF-kB signaling activation |
Reduced IL-6, PGE2, and NO release and protein level, IL-6, PTGES, COX-2, and NOS2 gene expression, and NF-κB nuclear translocation Reduction of inflammatory and degrading processes of OA damage |
| (Ha et al. 2015) |
NaHS (0.06–1.5 mM) dissolved in the culture medium, for 24 h + IL-1β (10 ng/mL) |
Human primary OA chondrocytes | NaHS | Osteoarthritis |
COX-2, iNOS, MMP-13; ERK/IκBα/NF-κB signaling activation |
Reduced COX-2, iNOS, MMP-13 release and gene expression; Inhibited ERK/IκBα/NF-κB activation Reduction of degrading processes of OA damage |
| (Sieghart et al. 2015) |
NaHS (0.06–1 mmol/L) dissolved in the culture medium, for 1 h + IL-1β (10 ng/mL) |
Human primary OA fibroblast-like synoviocytes | NaHS | Osteoarthritis |
IL-6, IL-8; MMP-2, MMP-14; MAPK and Akt1/2/PI3K protein phosphorylation |
Reduced IL-6 and IL-8 secretion, MMP-2 and MMP-14 gene expression, and MAPK phosphorylation; Increased Akt1/2 phosphorylation Reduction of inflammatory and degrading processes of OA damage |
| (Vela-Anero et al. 2017) |
NaHS or GYY4137 (200 or 1000 μM) dissolved in the culture medium, for 21 days + IL-1β (5 ng/mL) |
Human OA cartilage disks | NaHS and GYY4137 | Osteoarthritis |
MMP-3, MMP-13; Col2a1, glycosaminoglycans, aggrecans |
Reduced MMP-3 and MMP-13 production, and increased Col2a1, glycosaminoglycans, and aggrecans synthesis Reduction of degrading processes of OA damage |
| (Fioravanti et al. 2013) |
25%, 50%, or 100% of Vetriolo thermal water dissolved in the culture medium, for 48 h + IL-1β (5 ng/mL) |
Human primary OA chondrocytes | Vetriolo thermal water (Trentino Alto Adige, Italy), strongly acidic sulfate, rich in calcium, magnesium and iron | Osteoarthritis |
NO, iNOS; Cell viability and apoptosis; Morphological assessment |
25%, 50% of Vetriolo water increased survival recovery rate, reduced NO levels, iNOS expressions, and apoptosis %; Enhanced morphological characteristics Reduction of degrading processes of OA damage |
| (Xu et al. 2011) |
NaHS (100 μM) dissolved in the culture medium, for 4 h + (H2O2) (400 μM) |
Murine osteoblast-like cell line (MC3T3-E1) | NaHS | Osteoporosis |
Viability, proliferation and apoptosis; NO, ALP, SOD, NADPH oxidase p38/ERK1/2/MAPKs activation |
Increased viability, cell proliferation, ALP and SOD activities; Decreased apoptosis, NO release and NADPH oxidase activity, and p38/ERK1/2/MAPKs activation Proliferative and antioxidant effects against osteoporosis damage |
| (Gambari et al. 2014) | NaHS (50–300 μM) dissolved in the culture medium, for 72 h to 6 days | Human differentiated osteoclasts | NaHS | Osteoporosis |
Osteoclasts differentiation; ROS production, NRF2, KEAP1, NQO1, and PRDX1 |
Decreased osteoclast differentiation, intracellular ROS levels; Upregulated NRF2 protein expression and nuclear translocation, and increased antioxidant gene expression Antioxidant effects against osteoporosis damage |
| (Lv et al. 2017) |
GYY4137 (100 μM) dissolved in the culture medium, for 4 h + (H2O2) (400 μM) |
Murine osteoblast-like cell line (MC3T3-E1) | GYY4137 | Osteoporosis |
Viability, proliferation, Runx2, and apoptosis; NO, ALP, and SOD ERK1/2 activation |
Increased viability, cell proliferation, ALP and SOD activities, and Runx2 gene expression; Decreased apoptosis, NO release, and ERK1/2 activation Proliferative and antioxidant effects against osteoporosis damage |
| (Liu et al. 2017) | NaHS (400 μmol/L) dissolved in the culture medium, for 12 h | Rat primary osteoblasts | NaHS | Osteoporosis |
Osteoblast proliferation and mineralization; Apoptosis; KATP protein expression |
Decreased cell proliferation, and increased the number of apoptotic cells, osteoblast mineralization, and KATP protein expression Reduction of osteoporosis damage |
NaHS natrium hydrogen sulfide, IL interleukin, RA rheumatoid arthritis, MAPK mitogen-activated protein kinase, ERK extracellular signal-regulated kinase, OA osteoarthritis, COX-2 cyclooxygenase 2, MMP metalloproteinase, C-28/I2 human chondrocyte cell line, NF-κB nuclear factor-κB, GYY4137 exogenous slow releasing H2S, LPS lipopolysaccharide, TNF-α tumor necrosis factor α, PGE2 prostaglandin E2, NO nitric oxide, iNOS inducible NO synthase, PTGES prostaglandin E synthase, IκBα inhibitor of κB, Akt protein kinase B, PI3K phosphoinositide 3-kinase, Col2a1 collagen type II alpha 1 chain, ALP alkaline phosphatase, SOD superoxide dismutase, NADPH nicotinamide adenine dinucleotide phosphate, ROS reactive oxygen species, NRF2 nuclear factor erythroid 2-related factor 2, Keap1 Kelch-like ECH-associated protein 1, NQO1 NADPH quinone dehydrogenase 1, PRDX1 peroxiredoxin 1, H2O2 hydrogen peroxide, MC3T3-E1 murine osteoblast-like cell line, Runx2 runt-related transcription factor 2, KATP ATP-sensitive potassium channels