Abstract
BackgroundOsteoarthritis (OA) is a kind of systemic musculoskeletal disorder and a most important factor for causing disability and physical painfulness. Nevertheless, due to the fact that OA can be triggered by multiple etiological factors, this disease is hard to be cured. Therefore, it is of great necessity for us to find novel targets or drugs for OA treatment.Materials and methodsThe chondrocytes were treated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP) to induce pyroptosis in OA. The cell proliferation was detected by Cell Counting Kit-8 assay (CCK-8 assay). Enzyme-linked immunosorbent assay (ELISA) was used for the detection of pyroptosis-related inflammatory factors. Then, the antagonists for gasdermin D (GSDMD) (disulfiram) and high mobility group box 1 (HMGB1) (glycyrrhizic acid) were used to treat the cell model to observe the effects of disulfiram and glycyrrhizic acid on the proliferation of chondrocytes in OA. The protein levels of pyroptosis-related inflammatory factors were measured by western blot, and the levels of aldehyde dehydrogenase (ALDH) and reactive oxygen species (ROS) were measured by corresponding commercial kits.ResultsAfter chondrocytes were induced by LPS and ATP, the cell proliferation was decreased and the expressions of pyroptosis-related inflammatory factors were increased. Disulfiram and glycyrrhizic acid treatment led to enhanced cell proliferation and increased expressions of pyroptosis-related inflammatory factors, while disulfiram showed better alleviative effects on the inflammation in chondrocytes in OA. However, co-treatment with disulfiram at a high concentration and glycyrrhizic acid did not result in higher proliferation of chondrocytes and alleviated inflammation, but led to oxidative stress.ConclusionIn conclusion, co-treatment with disulfiram and glycyrrhizic acid at a standard concentration suppresses the inflammatory response of chondrocytes, which may provide guidance for the use of the drugs in the treatment of OA.
Highlights
Osteoarthritis (OA) is a kind of systemic musculoskeletal disorder and a most important factor for causing disability and physical painfulness [1]
In conclusion, co-treatment with disulfiram and glycyrrhizic acid at a standard concentration suppresses the inflammatory response of chondrocytes, which may provide guidance for the use of the drugs in the treatment of OA
There is no direct research on the role of gasdermin D (GSDMD) and high mobility group box 1 (HMGB1) in chondrocytes of OA, and this study aims to use the antagonists for GSDMD and HMGB1 to treat the model of chondrocytes under the condition of pyroptosis, thereby investigating the synergistic effects and underlying mechanism of these two drugs on OA
Summary
Osteoarthritis (OA) is a kind of systemic musculoskeletal disorder and a most important factor for causing disability and physical painfulness [1] It is the most prevalent chronic joint disease that happens mainly in the elderly over 65, and recent studies have confirmed this disease as an immunopathological disease based on the spectrum between normal control and rheumatoid arthritis [2, 3]. Due to the fact that OA can be triggered by multiple etiological factors including aging, obesity, and a genetic predisposition, this disease is hard to be cured [5, 6] It is of great necessity for us to find novel targets or drugs for OA treatment. Osteoarthritis (OA) is a kind of systemic musculoskeletal disorder and a most important factor for causing disability and physical painfulness.
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