Could Oxidative Stress Regulate the Expression of MicroRNA-146a and MicroRNA-34a in Human Osteoarthritic Chondrocyte Cultures?

Abstract

Oxidative stress and the overproduction of reactive oxygen species (ROS) play an important role in the pathogenesis of osteoarthritis (OA). Accumulating evidence has demonstrated the involvement of microRNAs (miRNAs) dysregulation in disease development and progression. In this study, we evaluated the effect of oxidative stress on miR-146a and miR-34a expression levels in human OA chondrocytes cultures stimulated by H2O2. Mitochondrial ROS production and cell apoptosis were detected by flow cytometry. The antioxidant enzymes SOD-2, CAT, GPx, the transcriptional factor NRF2 and the selected miRNAs were analyzed by qRT-PCR. The H2O2-induced oxidative stress was confirmed by a significant increase in superoxide anion production and of the apoptotic ratio. Furthermore, H2O2 significantly up-regulated the expression levels of SOD-2, CAT, GPx and NRF2, and modulated miR-146a and miR-34a gene expression. The same analyses were carried out after pre-treatment with taurine, a known antioxidant substance, which, in our experience, counteracted the H2O2-induced effect. In conclusion, the induction of oxidative stress affected cell apoptosis and the expression of the enzymes involved in the oxidant/antioxidant balance. Moreover, we demonstrated for the first time the modification of miR-146a and miR-34a in OA chondrocytes subjected to H2O2 stimulus and we confirmed the antioxidant effect of taurine.

Taurine alleviates endoplasmic reticulum stress in the chondrocytes from patients with osteoarthritis

“…Whether such transcriptional regulation is lying behind alleviation of ER stress needs further research .Another thing needs more concern is the dose variability, which is relative common in clinical practice. The dose varies from 120 to 480 μM [31,32], while in our study the concentration of 25 mM taurine is the critical concentration which will do no apparent harm to chondrocyte viability. Such concentration is chosen to show the best characteristics its alleviation to ER stress.…”

“…Taurine could not only promote cell growth and maintain phenotype of human articular chondrocytes [29], but also ameliorate ROS-induced cartilage damage through its antioxidant property [15,30]. It is worth noting that a significant increase in NRF2 mRNA levels in the H 2 O 2 -stimulated chondrocyte is observed after treatment with taurine at a low concentration of 200 μM [31]. Whether such transcriptional regulation is lying behind alleviation of ER stress needs further research .Another thing needs more concern is the dose variability, which is relative common in clinical practice.…”

The effects of ultrasound exposure on P-glycoprotein-mediated multidrug resistance in vitro and in vivo

“…MiR-200c and miR-34a could be induced by oxidative stress in several cell types, and are designated as oxidative stress-responsive miRNAs [ 30 , 43 , 44 ]. In this study, we found that US radiation increased mir-200c and miR-34a expression through oxidative signal pathway, which was responsible for P-gp down-regulation.…”

Effect of oxidative stress and 3‐hydroxytyrosol on DNA methylation levels of miR‐9 promoters

“…2 Furthermore, H 2 O 2 supplementation has been shown to elicit oxidative stress in chondrocytes. 3,4 So far, innovative strategies of treatments with no side effects need to be elucidated. For this purpose, dietderived natural compounds raised a noteworthy interest due to their preventive and therapeutic action in OA.…”