Ageing and Osteoarthritis Synergically Affect Human Synoviocyte Cells: An In Vitro Study on Sex Differences

Osteoarthritis is a chronic inflammatory disease that affects all of the joints, especially those of the elderly. Aging is a natural and irreversible biological process implicated in the pathophysiology of many chronic diseases, such as osteoarthritis. Inflammation and oxidative stress are the main factors involved in osteoarthritis and aging, respectively, with the production of several pro-inflammatory cytokines such as Interleukin 1 beta (IL1 beta) and reactive oxygen species. The aim of the study was to set-up an in vitro model of osteoarthritis and aging, focusing on the sex differences by culturing male and female fibroblast-like synoviocytes (FLSs) with IL1 beta, hydrogen peroxide (H2O2), IL1 beta+H2O2 or a growth medium (control). IL1 beta+H2O2 reduced the cell viability and microwound healing potential, increased Caspase-3 expression and reactive oxygen species and IL6 production; IL1 beta increased IL6 production more than the other conditions did; H2O2 increased Caspase-3 expression and reactive oxygen species production; Klotho expression showed no differences among the treatments. The FLSs from female donors demonstrated a better response capacity in unfavorable conditions of inflammation and oxidative stress than those from the male donors did. This study developed culture conditions to mimic the aging and osteoarthritis microenvironment to evaluate the behavior of the FLSs which play a fundamental role in joint homeostasis, focusing on the sex-related aspects that are relevant in the osteoarthritis pathophysiology.

Automated summary

This study developed an in vitro model to mimic the microenvironment of aging and osteoarthritis and evaluated the differences between male and female fibroblast-like synoviocytes (FLSs). The results showed that FLSs from female donors demonstrated a better response capacity in unfavorable conditions of inflammation and oxidative stress.