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Gout is the most common inflammatory arthropathy of metabolic origin and it is characterized by intense inflammation, the underlying mechanisms of which are unknown.
According to this
study, the inflammation and pain experienced during an acute gout attack is
revealed which is formed as a result of oxidative role of monosodium urate crystals
in fibroblast-like synoviocytes. This model has paved way to resolute the role
of antioxidants involved in local and systemic damage to the joint in the
development of novel therapeutic targets to block OS.
Gout is the most
common inflammatory arthropathy of metabolic origin and it is characterized by
intense inflammation, the underlying mechanisms of which are unknown. The aim
of this study was to evaluate the oxidative stress in human fibroblast-like
synoviocytes (FLS) exposed to monosodium urate (MSU) crystals, which trigger an
inflammatory process.
Human FLS
isolated from synovial tissue explants were stimulated with MSU crystals (75
μg/mL) for 24 h. Cellular viability was evaluated by crystal violet staining,
apoptosis was assessed using Annexin V, and the cellular content of reactive
oxygen species (ROS) and nitrogen species (RNS) (O2 -, H2O2, NO) was assessed
with image-based cytometry and fluorometric methods. In order to determine
protein oxidation levels, protein carbonyls were detected through oxyblot
analysis, and cell ultrastructural changes were assessed by transmission
electron microscopy.
The viability of
FLS exposed to MSU crystals decreased by 30 % (P < 0.05), while apoptosis
increased by 42 % (P = 0.01). FLS stimulated with MSU crystals exhibited a
2.1-fold increase in H2O2 content and a 1.5-fold increase in O2 - and NO
levels. Oxyblots revealed that the spots obtained from FLS protein lysates exposed
to MSU crystals exhibited protein carbonyl immunoreactivity, which reflects the
presence of oxidatively modified proteins. Concomitantly, MSU crystals
triggered the induction of changes in the morphostructure of FLS, such as the
thickening and discontinuity of the endoplasmic reticulum, and the formation of
vacuoles and misfolded glycoproteins.
Our results prove
that MSU crystals induce the release of ROS and RNS in FLS, subsequently
oxidizing proteins and altering the cellular oxidative state of the endoplasmic
reticulum, which results in FLS apoptosis.
Arthritis research and therapy
Monosodium urate crystals induce oxidative stress in human synoviocytes
Yessica Zamudio-Cuevas et al.
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