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.
Highlights
Osteoarthritis (OA) is the most common degenerative joint disorder and it represents the main cause of pain, functional impairment and disability in adult and elderly populations [1]
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
In this study we observed the effect of H2O2-induced oxidative stress on the transcriptional levels of the main factors responsible for the maintenance of homeostatic oxidant/antioxidant equilibrium in human OA chondrocyte cultures
Summary
Osteoarthritis (OA) is the most common degenerative joint disorder and it represents the main cause of pain, functional impairment and disability in adult and elderly populations [1]. OA affects the whole joint structure and it is characterized by the progressive degradation of the components of articular cartilage, thickening of subchondral bone and synovial inflammation, inducing the loss of normal joint architecture and function [2]. The release of reactive oxygen species (ROS), such as superoxide anion, hydrogen peroxide (H2O2) and nitric oxide, contributes to cartilage damage and a concomitant low-grade chronic inflammation [3]. ROS are free radicals containing oxygen molecules derived from cellular oxidative metabolism including enzyme activities and mitochondrial respiration, and play a pivotal role in many cellular functions. In OA chondrocytes, ROS overproduction causes DNA damage. Oxidative radical accumulation in the joint contributes to the inhibition of glycosaminoglycan and collagen synthesis and to the activation of metalloproteinases and aggrecanases, promoting cartilage breakdown [5]. It has been reported that chondrocytes apoptosis related to OA can be induced by oxidative stress [6]
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