Soluble inflammatory mediators of synoviocytes stimulated by monosodium urate crystals induce the production of oxidative stress, pain, and inflammation mediators in chondrocytes

Abstract

We hypothesized that the secretion of inflammatory mediators from synoviocytes affects the chondrocyte homeostasis of articular cartilage. This study was a preliminary attempt to elucidate the molecular mechanisms by which soluble mediators obtained from activated synoviocytes induce oxidative stress and inflammation in chondrocytes. We measured the concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), nerve growth factor (NGF), superoxide anion (O 2•− ), hydrogen peroxide (H 2 O 2 ), and nitric oxide (NO • ) from articular human cells. First, we created a conditional basal medium by exposing synoviocytes (HS) to monosodium urate crystals (CBM). The chondrocytes were exposed to either CBM (CCM), urate crystals directly (CMSU), or remained untreated (CC) as a negative control. Data were analyzed by ANOVA tests; Bonferroni test was performed for multiple comparisons between groups. Interestingly, we observed that mediators of inflammation and oxidative stress were significantly higher in CCM than CMSU and CC groups (P<0.01). The specific concentrations were as follows: 19.85 ng/mL of IL-6, 9.79 ng/mL of IL-8, 5.17 ng/mL of NGF, and 11.91 ng/mL of MCP-1. Of note, we observed the same trend for reactive oxygen and nitrogen species (P<0.001). Soluble mediators secreted by synoviocytes after being activated with MSU crystals (as observed in individuals who present gout attacks) trigger chondrocyte activation intensifying the articular inflammatory, oxidative, and pain states that damage cartilage in OA; this damage is more severe even when compared to HC directly exposed to monosodium urate crystals.

An Exponential Curve Relationship Between Serum Urate and Migraine: A Cross-Section Study From NHANES

“…Furthermore, we also suggest that there is a threshold effect on the neuroprotective effect and that the infliction point might be 7.8 mg/dl. Besides, the underlining mechanism might be that MSU crystal formed might trigger inflammation via IL-1b, TNF-a, IL-6, IL-8, and oxidative stress (27)(28)(29)(30)(31).…”

Spatiotemporal Observation of Monosodium Urate Crystals Deposition in Synovial Organoids Using Label-Free Stimulated Raman Scattering

“…Previous researches have shown that synoviocytes, when stimulated by MSU crystals, can secrete proinflammatory mediators [ 15 , 16 ]. These mediators then activated chondrocytes and immune cells, intensifying synovial inflammation and oxidative and pain states [ 7 , 17 ]. The mechanisms by which MSU crystals interact with synovial tissues in gout have garnered increasing attention and are crucial for guiding future therapies.…”

The protective effects of S14G-humanin (HNG) against mono-sodium urate (MSU) crystals- induced gouty arthritis

“…MDA is the terminal product of lipid peroxidation which reflects the degree of disruption induced by ROS [ 28 ]. Recently, the activation of oxidative stress has been reported to be involved in the pathological changes in gout induced by MSU crystals [ 29 ]. In the present study, we found that the activation of oxidative stress in BMDMs was significantly induced by stimulation with MSU crystals, accompanied by the upregulation of NOX-4, an important mediator of oxidative stress [ 30 ].…”