Hyperlipidemic microenvironment conditionates damage mechanisms in human chondrocytes by oxidative stress

Abstract

BackgroundCurrently, two pathogenic pathways describe the role of obesity in osteoarthritis (OA); one through biomechanical stress, and the other by the contribution of systemic inflammation. The aim of this study was to evaluate the effect of free fatty acids (FFA) in human chondrocytes (HC) expression of proinflammatory factors and reactive oxygen species (ROS).MethodsHC were exposed to two different concentrations of FFA in order to evaluate the secretion of adipokines through cytokines immunoassays panel, quantify the protein secretion of FFA-treated chondrocytes, and fluorescent cytometry assays were performed to evaluate the reactive oxygen species (ROS) production.ResultsHC injury was observed at 48 h of treatment with FFA. In the FFA-treated HC the production of reactive oxygen species such as superoxide radical, hydrogen peroxide, and the reactive nitrogen species increased significantly in a at the two-dose tested (250 and 500 μM). In addition, we found an increase in the cytokine secretion of IL-6 and chemokine IL-8 in FFA-treated HC in comparison to the untreated HC.ConclusionIn our in vitro model of HC, a hyperlipidemia microenvironment induces an oxidative stress state that enhances the inflammatory process mediated by adipokines secretion in HC.

Fatty Acids and Oxylipins in Osteoarthritis and Rheumatoid Arthritis—a Complex Field with Significant Potential for Future Treatments

“…It was proposed that the 16:0-induced lipotoxicity could be prevented through the sequestration of excess free FA within these lipid droplets. In other studies, co-incubation of 16:0 and 18:1n-9 increased the production of IL-6, IL-8, and reactive oxygen species, as well as apoptosis [ 67 , 68 ]. Once again, there remains some controversy further emphasizing the complex nature of lipidology in joint diseases.…”

“…In chondrocytes or cartilage explants of animal and human origin, 16:0 was documented to induce the expression of cyclooxygenase (COX)-2 and inducible NO synthase (iNOS), IL-6 release, endoplasmic reticulum stress, apoptosis, proteoglycan (PG)/glycosaminoglycan (GAG) loss, extracellular matrix (ECM) degradation, and cartilage breakdown [ 26 , 63 – 66 ]. It can also produce some of these effects together with 18:1n-9 [ 67 , 68 ]. However, once again the results are not totally consistent, as opposite data exist reporting reduced GAG release and cartilage breakdown [ 69 ] or no response to 16:0 exposure [ 70 ].…”

Emerging Players at the Intersection of Chondrocyte Loss of Maturational Arrest, Oxidative Stress, Senescence and Low‐Grade Inflammation in Osteoarthritis

“…The dose-dependent increased release of reactive oxygen and nitrogen species (ROS and RNS) and inflammatory cytokines by chondrocytes exposed to mixtures of free fatty acids (FFA) including palmitate has been recently shown in vitro [ 52 ] and OA development in rats fed with high-SFA diet has been reported in vivo [ 53 ] (see Figure 2 ). Palmitate has also proapoptotic and proinflammatory activities [ 54 ] that are reduced after inhibition of Toll-like receptor (TLR) 4.…”

NLRP3 Inflammasome: The Stormy Link Between Obesity and COVID-19

“…The WHO defines obesity as a complex entity in which there is an excessive accumulation of fat that affects practically all body functions and compromises the individual's health (1). Furthermore, obesity is considered the fifth risk factor for mortality, as it is the main risk factor of diabetes, cardiovascular disease, hypertension, dyslipidemia, musculoskeletal disorders such as osteoarthritis, and other diseases (3)(4)(5). It is well known that obesity leads to a low-grade chronic inflammation promoted by the release of adipokines and cytokines (6).…”