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Updated: Jul 4, 2026

Ameliorating Osteoarthritis in Mice Using Silver Nanoparticles
Published on: June 2, 2023
Okanin alleviates osteoarthritis by suppressing oxidative stress and pyroptosis via Nrf2/HO-1 activation
1Orthopedic Department, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China; Enze Medical Research Center, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China.
Abstract:
Osteoarthritis (OA) is a chronic joint disorder characterized by degenerative cartilage and chondrocyte dysfunction. Oxidative stress and NLRP3 inflammasome-mediated pyroptosis play pivotal roles in OA progression. This study investigated the protective effects and mechanisms of Okanin, a natural flavonoid, in a mouse model of knee osteoarthritis. We found that Okanin effectively activated the Nrf2/HO-1 signaling pathway, significantly enhanced the antioxidant capacity of chondrocytes and scavenged excess ROS. Concurrently, Okanin inhibited the assembly and activation of the NLRP3 inflammasome, thereby suppressing the caspase-1/GSDMD-dependent pyroptosis pathway. In vivo experiments demonstrated that Okanin treatment improved articular cartilage morphology, reduced proteoglycan loss, and decreased OARSI scores in a destabilization of the medial meniscus (DMM) murine model. Mechanistically, Nrf2 was identified as a key target of Okanin through siRNA knockdown. This study is the first to reveal that Okanin exerts dual chondroprotective effects against oxidative stress and pyroptosis via the Nrf2/HO-1 axis, suggesting a novel strategy for OA treatment.
Insights
Okanin, a natural flavonoid, protects against osteoarthritis by reducing oxidative stress and cell death. It activates the Nrf2/HO-1 pathway and inhibits NLRP3 inflammasome-mediated pyroptosis, offering a novel treatment strategy for joint disorder.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Osteoarthritis (OA) is a degenerative joint disease.
- Oxidative stress and NLRP3 inflammasome-mediated pyroptosis contribute to OA.
- Current OA treatments have limitations.
Purpose of the Study:
- Investigate Okanin's protective effects in a mouse model of knee osteoarthritis.
- Elucidate the mechanisms underlying Okanin's chondroprotective action.
- Explore Okanin as a potential therapeutic agent for OA.
Main Methods:
- Utilized a destabilization of the medial meniscus (DMM) murine model for OA induction.
- Assessed Okanin's impact on oxidative stress markers (ROS) and chondrocyte function.
- Examined the Nrf2/HO-1 and NLRP3 inflammasome/caspase-1/GSDMD pathways.
- Analyzed articular cartilage morphology and proteoglycan content.
Main Results:
- Okanin activated the Nrf2/HO-1 pathway, enhancing antioxidant capacity and scavenging ROS.
- Okanin inhibited NLRP3 inflammasome assembly and caspase-1/GSDMD-dependent pyroptosis.
- In vivo, Okanin improved cartilage structure, reduced proteoglycan loss, and lowered OARSI scores.
- Nrf2 was confirmed as a key target of Okanin.
Conclusions:
- Okanin demonstrates dual chondroprotective effects against oxidative stress and pyroptosis.
- The Nrf2/HO-1 signaling pathway is crucial for Okanin's mechanism of action.
- Okanin represents a promising novel therapeutic strategy for osteoarthritis treatment.
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