Oleic and linoleic acids induce oxidative stress in chondrocytes by inhibiting autophagy‐regulated ciliogenesis
View(2024)
Abstract
Abstract The lack of a cure for osteoarthritis (OA), a prevalent joint disease among older individuals, remains an ongoing challenge. Obesity is a common risk factor for OA. Chondrocyte autophagy plays a crucial role in delaying the onset of OA. Our previous studies have demonstrated a significant elevation in the levels of oleic acid (OLA) and linoleic acid (LA) in the synovial fluid (SF) of patients with OA and obesity compared to those with OA alone, and an inhibitory effect of these molecules on the activation of autophagy. Accumulating evidence indicates a reciprocal regulatory relationship between autophagy and ciliogenesis; however, whether autophagy‐mediated ciliogenesis plays a significant role in the pathogenesis of OA remains unclear. In this study, we aimed to determine whether OLA and LA affect OA development via the regulation of chondrocyte autophagy‐mediated ciliogenesis. We found that both molecules inhibited this process in chondrocytes. Moreover, intracellular calcium and reactive oxygen species (ROS) levels increased simultaneously. Further, we explored the relationship between autophagy and ciliogenesis in chondrocytes. Activation of autophagy by rapamycin significantly attenuated the ciliogenesis inhibition caused by OLA and LA. Importantly, the downregulation of AKT and mTOR expression in chondrocytes reversed the autophagy‐mediated inhibition of ciliogenesis and the ROS‐accumulation‐mediated inflammation induced by OLA and LA. Taken together, our results suggest that OLA and LA induce calcium‐overload‐driven ROS accumulation via autophagy‐mediated ciliogenic disorders during OA pathogenesis. These findings demonstrate that targeting autophagy and ciliogenesis in chondrocytes is a protective strategy in the OA pathogenesis induced by OLA and LA.
MoreTranslated text
Key words
autophagy,ciliogenesis,linoleic acid,oleic acid,osteoarthritis,reactive oxygen species
AI Read Science
Must-Reading Tree
Example
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined