Abstract
Oxidative stress (OS) has been linked to the aetiology of many diseases including osteoarthritis (OA). Recent studies have shown that caveolin-1—a structural protein of plasma membrane’s caveolae—is upregulated in response to OS. Here, we explore the function of caveolin-1 in chondrocytes derived from healthy individuals (control) and OA patients that were subjected to exogenous OS. We showed that caveolin-1 was upregulated in response to acute OS in the control, but not in OA chondrocytes. Moreover, OS-induced DNA damage analysis revealed that control cells started repairing the DNA lesions 6 h post-oxidative treatment, while OA cells seemed unable to restore these damages. Importantly, in the control cells, we observed a translocation of caveolin-1 from the membrane/cytoplasm in and out of the nucleus, which coincided with the appearance and restoration of DNA lesions. When caveolin-1 was prevented from translocating to the nucleus, the control cells were unable to repair DNA damage. In OA cells, no such translocation of caveolin-1 was observed, which could account for their inability to repair DNA damage. Taken together, these results provide novel insights considering the role of caveolin-1 in response to OS-induced DNA damage while revealing its implication in the pathophysiology of OA.
Highlights
The imbalance between the production and scavenging of reactive oxygen species (ROS) is referred to as oxidative stress (OS)
We found that caveolin-1 mRNA and protein levels were significantly elevated in OA chondrocytes compared to the control cells under normal conditions
A series of studies have shown that oxidative stress (OS) occurs with ageing in the articular cartilage and this promotes the development of osteoarthritis (OA)
Summary
The imbalance between the production and scavenging of reactive oxygen species (ROS) is referred to as oxidative stress (OS). Especially DNA, is considered as a causal factor for cellular senescence and organismal ageing and has been associated with several age-relates diseases [2]. Osteoarthritis (OA), the most common age-related disease [3], has been linked to chondrocyte senescence as well as to OS [4,5]. As our group and others have demonstrated, OS could lead to mitochondrial dysfunction, which will in turn amplify ROS accumulation, comprising a vicious loop that promotes OA pathogenesis [6,7]. Previous studies examining OS response have revealed that sublethal doses of exogenous oxidative insult results in upregulation of caveolin-1 protein levels [8,9].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
