Defective RuO₂ Nanospheres Attenuate Osteoarthritis Progression via Suppressing the ROS/NLRP3/Caspase-1 Signaling...

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.