gyy-4137 and Osteoarthritis

Rheumatoid arthritis (RA) and osteoarthritis (OA) are widespread rheumatic diseases characterized by persistent inflammation and joint destruction. Hydrogen sulfide (H2S) is an endogenous gas with important physiologic functions in the brain, vasculature and other organs. Recent studies have found H2S to be a mediator in inflammatory joint diseases.. This review summarizes the recent literature in this area highlighting relevant developments.. Several authors have found that H2S exhibited anti-inflammatory, anti-catabolic and/or anti-oxidant effects in rodent models of acute arthritis and in in vitro models using human synoviocytes and articular chondrocytes from RA and OA tissues. The earliest studies used fast-dissolving salts, such as NaSH, but GYY4137, which produces H2S more physiologically, shortly appeared. More recently still, new H2S-forming compounds that target mitochondria have been synthesized. These compounds open exciting opportunities for investigating the role of H2S in cell bioenergetics, typically altered in arthritides. Positive results have also been obtained when H2S is administered as a sulphurous water bath, an option meriting further study. These findings suggest that exogenous supplementation of H2S may provide a viable therapeutic option for these diseases, particularly in OA.

Topics: Animals; Arthritis, Rheumatoid; Cells, Cultured; Clinical Trials as Topic; Disease Models, Animal; Humans; Hydrogen Sulfide; Morpholines; Organothiophosphorus Compounds; Osteoarthritis; Sulfides; Treatment Outcome

Type 2 diabetes (DB) is an independent risk factor for osteoarthritis (OA). However, the mechanisms underlying the connection between both diseases remain unclear. Synovial macrophages from OA patients with DB present a marked pro-inflammatory phenotype. Since hydrogen sulphide (H

Topics: Diabetes Mellitus, Type 2; Humans; Hydrogen Sulfide; Macrophages; Osteoarthritis; Phenotype

Osteoarthritis (OA) is the most common articular chronic disease. However, its current treatment is limited and mostly symptomatic. Hydrogen sulfide (H

Topics: Animals; Arthralgia; Cartilage, Articular; Cyclooxygenase 2; Disease Models, Animal; Female; Gene Expression Regulation; Hydrogen Sulfide; Injections, Intra-Articular; Matrix Metalloproteinase 13; Morpholines; Motor Activity; NF-E2-Related Factor 2; Nitric Oxide Synthase Type II; Organothiophosphorus Compounds; Osteoarthritis; Oxidative Stress; Protective Agents; Rats; Rats, Wistar; Rotarod Performance Test; Signal Transduction; Treatment Outcome

Hydrogen sulfide (H2S), the third gasotransmitter together with NO and CO, is emerging as a regulator of inflammation. To test if it might offer therapeutic value in the treatment of osteoarthritis (OA) we evaluated the effects of two exogenous sources of H2S, NaSH and GYY4137, on inflammation and catabolic markers that characterize OA.. Human chondrocytes (CHs) were isolated from OA tissue. Cells were stimulated with a pro-inflammatory cytokine (interleukin-1β, IL1β, 5 ng/ml) and the ability of the two H2S sources to ameliorate its effects on the cells was tested. Nitric oxide (NO) production was quantified through the Griess reaction. Protein levels of inducible NO synthase (NOS2) and matrix metalloproteinase 13 (MMP13) were visualized through immunocytochemistry (ICC). Relative mRNA expression was quantified with qRT-PCR. Prostaglandin-2 (PGE-2), interleukin 6 (IL6) and MMP13 levels were measured with specific EIAs. NFκB nuclear translocation was visualized with immunofluorescence.. Both H2S sources led to significant reductions in NO, PGE-2, IL6 and MMP13 released by the cells and at the protein level. This was achieved by downregulation of relevant genes involved in the synthesis routes of these molecules, namely NOS2, cyclooxigenase-2 (COX2), prostaglandin E synthase (PTGES), IL6 and MMP13. NFκB nuclear translocation was also reduced.. NaSH and GYY4137 show anti-inflammatory and anti-catabolic properties when added to IL1β activated osteoarthritic CHs. Supplementation with exogenous H2S sources can regulate the expression of relevant genes in OA pathogenesis and progression, counteracting IL1β pro-inflammatory signals that lead to cartilage destruction in part by reducing NFκB activation.

Topics: Aged; Aged, 80 and over; Biomarkers; Cartilage, Articular; Cells, Cultured; Chondrocytes; Dinoprostone; Female; Humans; Hydrogen Sulfide; Inflammation; Interleukin-1beta; Interleukin-6; Male; Matrix Metalloproteinase 13; Metabolism; Morpholines; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase; Organothiophosphorus Compounds; Osteoarthritis; Sulfides