Abstract
Scope: Osteoarthritis (OA) is a progressive disease characterized by cartilage degradation. Astaxanthin (Ast), a natural compound with remarkable antioxidant activity and multiple medical applications due to its activation of Nrf2 signaling, has been studied for application to various degenerative diseases. Currently, however, little is known about its efficacy in treating OA. This study reports the effects of Ast on cartilage homeostasis in OA progression.Methods: IL-1β, TNF-α, and tert-butyl hydroperoxide (TBHP) were used to impair cartilage homeostasis. Modulating effects of Ast on the Nrf2 signaling pathway, and damage-associated events including extracellular matrix (ECM) degradation, inflammation, oxidative stress, chondrocyte apoptosis, and in vivo cartilage degradation were examined.Results: Ast attenuated ECM degradation of OA chondrocytes through the Nrf2 signaling, and ameliorated the IL-1β-induced inflammatory response and ECM degradation via blockade of MAPK signaling. Additionally, Ast alleviated TNF-α-induced ECM degradation and chondrocyte apoptosis by inhibiting the NF-κB signaling, suppressed TBHP-induced oxidative stress, and subsequently reduced chondrocyte apoptosis. In vitro results were finally corroborated in vivo by demonstrating that Ast attenuates the severity of cartilage destruction in a mouse model of OA.Conclusions: Ast could protect against osteoarthritis via the Nrf2 signaling, suggesting Ast might be a potential therapeutic supplement for OA treatment.
Highlights
Osteoarthritis (OA), a common degenerative disorder affecting more than 240 million people, is a primary cause of disability [1]
We examined the effect of Ast on the chondrocyte proliferation
Inflammation and oxidative stress are closely related in OA progression
Summary
Osteoarthritis (OA), a common degenerative disorder affecting more than 240 million people, is a primary cause of disability [1]. Once cartilage homeostasis is disrupted, damage-associated signals will be transduced and amplified by a feed-forward loop, which leads to degradation and loss of cartilage [4] Many of these OA factors can induce low-grade chronic inflammation, and imbalance in oxidant–antioxidant levels, stimulating chondrocytes to produce reactive oxygen species (ROS) and proinflammatory cytokines including IL-1β, and TNF-α. These mediators are second messengers in intracellular signaling pathways that regulate the expression of the target genes encoding matrix degrading enzymes. Oxidative stress caused by H2O2 could induce ECM degradation and result in chondrocyte apoptosis [8] These mediators have overlapping effects, but each has its own role in mediating OA pathogenesis. It is relevant to use these mediators to induce OA in vitro to explore the pathogenesis of OA, and investigate possible therapeutic approaches
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
