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Ameliorating Osteoarthritis in Mice Using Silver Nanoparticles
Published on: June 2, 2023
Phycocyanin-functionalized selenium nanoparticles attenuate osteoarthritis through ferroptosis suppression and
Jiawei Hu1, Peng Luo1,2,3,4, Wei Zhang1
1Orthopedic Hospital, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Abstract:
Osteoarthritis (OA) is a widespread degenerative disorder of the joints, in which chondrocyte oxidative stress, inflammatory responses, and ferroptosis play pivotal roles in disease progression, yet current therapeutic strategies remain largely insufficient. In this study, we developed Se@PC NPs as a nanotherapeutic and assessed its efficacy against OA by leveraging selenium's role in redox regulation and ferroptosis inhibition along with phycocyanin's dual antioxidant and anti-inflammatory properties. The resultant Se@PC NPs demonstrated excellent stability and biocompatibility. In IL-1β-stimulated ATDC5 cells, they effectively scavenged reactive oxygen species (ROS), suppressed iron accumulation and lipid peroxidation, and upregulated key ferroptosis-related proteins (GPX4 and SLC7A11). Se@PC NPs can also promote the synthesis of cartilage extracellular matrix by reducing the levels of pro-inflammatory cytokines and catabolic enzymes. Transcriptomic analysis revealed that Se@PC NPs modulate the MAPK signaling pathway, as well as pathways associated with ferroptosis and oxidative stress. Furthermore, Se@PC NPs preserved mitochondrial structural integrity and membrane potential, thereby alleviating mitochondrial dysfunction. In a murine model of destabilization of the medial meniscus (DMM), Se@PC NPs attenuated cartilage erosion and osteophyte formation, restored the expression of COL2A1 and GPX4, suppressed MMP13 and COX2. In summary, Se@PC NPs synergistically exert antioxidant, anti-ferroptotic, and anti-inflammatory effects, effectively delaying OA progression and presenting a promising nanotherapeutic strategy.
Insights
Selenium and phycocyanin nanoparticles (Se@PC NPs) offer a novel treatment for osteoarthritis (OA). These nanoparticles combat oxidative stress, ferroptosis, and inflammation, effectively slowing disease progression in cellular and animal models.
Area of Science:
- Biomedical Engineering
- Nanomedicine
- Osteoarthritis Research
Background:
- Osteoarthritis (OA) is a degenerative joint disease driven by oxidative stress, inflammation, and ferroptosis.
- Current OA therapies are insufficient, highlighting the need for novel treatment strategies.
Purpose of the Study:
- To develop and evaluate selenium and phycocyanin nanoparticles (Se@PC NPs) as a nanotherapeutic for OA.
- To investigate the antioxidant, anti-ferroptotic, and anti-inflammatory mechanisms of Se@PC NPs in OA.
Main Methods:
- In vitro studies using IL-1β-stimulated ATDC5 cells to assess ROS scavenging, iron suppression, and ferroptosis marker modulation.
- Transcriptomic analysis to identify modulated signaling pathways (e.g., MAPK).
- In vivo studies using a murine destabilization of the medial meniscus (DMM) model to evaluate therapeutic efficacy.
Main Results:
- Se@PC NPs demonstrated stability and biocompatibility, effectively reducing oxidative stress, ferroptosis markers (GPX4, SLC7A11), and inflammation in vitro.
- Se@PC NPs modulated MAPK signaling, preserved mitochondrial function, and promoted cartilage matrix synthesis.
- In vivo, Se@PC NPs attenuated cartilage erosion, osteophyte formation, and modulated key OA-related gene expressions (COL2A1, GPX4, MMP13, COX2).
Conclusions:
- Se@PC NPs exhibit synergistic antioxidant, anti-ferroptotic, and anti-inflammatory effects.
- Se@PC NPs represent a promising nanotherapeutic strategy for delaying OA progression.
- This approach offers a novel avenue for OA treatment by targeting multiple disease pathways.