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Ameliorating Osteoarthritis in Mice Using Silver Nanoparticles
Published on: June 2, 2023
Defective RuO2 Nanospheres Attenuate Osteoarthritis Progression via Suppressing the ROS/NLRP3/Caspase-1 Signaling
Jie Lv1,2,3, Faheem Muhammad4,5, Zheng Wang1,2,3
1Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, Jiangsu 210008, PR China.
Abstract:
Osteoarthritis (OA) is the most prevalent degenerative joint disorder, characterized by chronic inflammation, cartilage degeneration, and the formation of osteophytes, which leads to serious economic and social challenges. Previous studies have demonstrated that oxidative stress-driven inflammation plays a crucial role in the pathophysiological progression of OA. In this study, we presented defective RuO2 (d-RuO2) as an effective antioxidant for the treatment of OA. Unlike the crystalline RuO2, the amorphous hydrous RuO2 nanospheres (composed of self-assembled ultrasmall RuO2) displayed superior nanozymatic antioxidant activities. In vitro studies demonstrated that d-RuO2 significantly reduced intracellular levels of reactive oxygen species (ROS), and decreased the expression of key inflammatory markers including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), indicating its anti-inflammatory effects. In vivo experiments showed that d-RuO2 effectively relieved pain, improved physical activity, and mitigated synovitis, cartilage degeneration, and bone remodeling induced by destabilization of the medial meniscus (DMM). Furthermore, the mechanistic investigations indicated that d-RuO2 attenuated the progression of OA by suppressing the ROS/NLRP3/Caspase-1 signaling pathway. In conclusion, we presented d-RuO2 as an efficient ROS scavenger, providing a potential therapeutic strategy for OA.
Insights
Defective ruthenium dioxide (d-RuO2) nanospheres effectively combat osteoarthritis by reducing oxidative stress and inflammation. This novel antioxidant therapy alleviates pain and joint degeneration in preclinical models.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Rheumatology
Background:
- Osteoarthritis (OA) is a prevalent degenerative joint disorder driven by oxidative stress and inflammation.
- Current treatments for OA face limitations in addressing its complex pathophysiology.
Purpose of the Study:
- To investigate the therapeutic potential of defective ruthenium dioxide (d-RuO2) nanospheres as an antioxidant for OA treatment.
- To evaluate the anti-inflammatory and disease-modifying effects of d-RuO2 in OA models.
Main Methods:
- Synthesis and characterization of amorphous hydrous RuO2 nanospheres (d-RuO2).
- In vitro assessment of d-RuO2's antioxidant and anti-inflammatory effects on cellular markers of oxidative stress and inflammation.
- In vivo evaluation of d-RuO2's efficacy in a destabilization of the medial meniscus (DMM) mouse model of OA, assessing pain, physical activity, and joint pathology.
- Mechanistic studies to elucidate the signaling pathways affected by d-RuO2 treatment.
Main Results:
- d-RuO2 demonstrated superior nanozymatic antioxidant activity compared to crystalline RuO2.
- In vitro studies showed d-RuO2 significantly reduced reactive oxygen species (ROS) and key inflammatory markers (iNOS, COX2, TNF-α, IL-1β).
- In vivo experiments revealed d-RuO2 effectively relieved pain, improved mobility, and reduced synovitis, cartilage degeneration, and bone remodeling in DMM mice.
- Mechanistic investigations indicated d-RuO2 suppressed the ROS/NLRP3/Caspase-1 signaling pathway.
Conclusions:
- d-RuO2 acts as an efficient ROS scavenger with significant anti-inflammatory properties.
- d-RuO2 presents a promising therapeutic strategy for mitigating osteoarthritis progression.
- The findings highlight the potential of nano-engineered ruthenium dioxide for treating degenerative joint diseases.

