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Updated: May 5, 2026

Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
Constructing Dual-Atomic Fe─Fe Sites Nanozyme for Targeted Osteoarthritis Therapy through Mitigating Oxidative Stress
Ting Ying1, Qi Wang2, Dejian Li2
1Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai, 200092, China.
Abstract:
Osteoarthritis progression is driven by excessive reactive oxygen species (ROS), which causes significant secondary damage to chondrocytes and articular cartilage. Herein, the concept of holding desired dual-site nanozymes is proposed through developing Fe─Fe dimers on nitrogen-doped porous carbon (Fe2-NCs) to eliminate excessive ROS through the co-adsorption mechanism of superoxide radical. The Fe2-NCs present an enhanced ROS performance, effectively mimicking key antioxidant enzymes. Density functional theory calculations indicate that the synergistic effects of the Fe─Fe dimer can modulate oxygen adsorption configurations and accelerating O─O bond-cleavage. In vitro and in vivo results show that Fe2-NCs effectively mitigate ROS, protecting chondrocytes from oxidative stress-induced apoptosis. The mitochondrial function can be strengthened over Fe2-NCs by inhibiting NOX4 expression, restoring ATP levels, and normalizing COXIV expression. Additionally, Fe2-NCs significantly downregulate the pro-inflammatory mediator COX-2, inhibit MMP-13-mediated cartilage degradation, and slow down the type II collagen (COL2) breakdown through the inhibition of NF-κB signaling pathway.
Insights
This study introduces novel nanozymes (Fe2-NCs) that neutralize harmful reactive oxygen species (ROS) to protect cartilage and chondrocytes, offering a new therapeutic strategy for osteoarthritis.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Biochemistry
Background:
- Osteoarthritis (OA) progression is exacerbated by excessive reactive oxygen species (ROS), leading to chondrocyte and articular cartilage damage.
- Current treatments often fail to address the underlying oxidative stress driving OA pathogenesis.
Purpose of the Study:
- To develop novel dual-site nanozymes, Fe─Fe dimers on nitrogen-doped porous carbon (Fe2-NCs), for effective ROS scavenging.
- To investigate the therapeutic potential of Fe2-NCs in mitigating oxidative stress and protecting against OA progression.
Main Methods:
- Synthesis of Fe2-NCs with dual-site nanozyme activity.
- Utilizing co-adsorption mechanisms for superoxide radical elimination.
- Employing Density Functional Theory (DFT) for mechanistic insights.
- Conducting in vitro and in vivo experiments to assess efficacy.
Main Results:
- Fe2-NCs demonstrated enhanced ROS scavenging, mimicking antioxidant enzymes.
- DFT calculations revealed synergistic Fe─Fe dimer effects accelerating O─O bond cleavage.
- Fe2-NCs protected chondrocytes from apoptosis, improved mitochondrial function, and normalized key protein expressions (NOX4, ATP, COXIV).
- Fe2-NCs inhibited pro-inflammatory mediators (COX-2), cartilage-degrading enzymes (MMP-13), and collagen breakdown via the NF-κB pathway.
Conclusions:
- Fe2-NCs represent a promising nanozyme strategy for OA treatment by effectively combating oxidative stress.
- The developed nanozymes offer multi-faceted protection against OA pathogenesis, including chondrocyte survival and cartilage preservation.

