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Updated: Apr 22, 2026
Ameliorating Osteoarthritis in Mice Using Silver Nanoparticles
Published on: June 2, 2023
Nanoplastics exposure accelerates the progression of osteoarthritis via lysosomal destabilization-mediated pyroptosis
Tanxin Yu1, Hanwen Zhang1, Weiqian Sun1
1Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325088, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou 325035 Zhejiang Province, China.
Introduction:
Nanoplastics (NPs), as emerging environmental pollutants, are increasingly detected in human musculoskeletal tissues, but their impact on osteoarthritis (OA) pathogenesis remains unclear.
Objectives:
This study aimed to investigate whether NPs exposure accelerates osteoarthritis progression in osteoarthritic mice, to elucidate the underlying molecular mechanisms, and to evaluate the therapeutic potential of quercetin.
Methods:
OA was induced in C57BL/6 mice via destabilization of the medial meniscus (DMM), with or without exposure to 20-nm polystyrene NPs (0.5 mg/mL in drinking water). For therapeutic intervention, quercetin (25 or 50 mg/kg) or indomethacin (3 mg/kg) was administered daily. Cartilage destruction was assessed by histology using the Osteoarthritis Research Society International (OARSI) scoring system, immunohistochemistry, and X-ray. In vitro, primary murine chondrocytes were treated with NPs and/or quercetin. Mechanisms were investigated using transmission electron microscopy, immunofluorescence, Western blot, organelle staining, and siRNA knockdown.
Results:
NPs exposure significantly accelerated cartilage degradation and OA progression in DMM mice. Internalized NPs accumulated in chondrocyte lysosomes, inducing lysosomal membrane permeabilization (LMP), cathepsin B release, and subsequent NLRP3 inflammasome activation, leading to pyroptosis (evidenced by cleavage of gasdermin D N-terminal, GSDMD-N) and extracellular matrix loss. Quercetin restored lysosomal integrity, inhibited the LMP-NLRP3-pyroptosis axis in chondrocytes, and markedly attenuated NPs-aggravated cartilage destruction in vivo.
Conclusion:
This study identifies nanoplastics as novel environmental risk factors that act as pathological amplifiers in the context of osteoarthritis by inducing lysosomal destabilization-mediated pyroptosis in chondrocytes. Quercetin alleviates this pathological cascade by stabilizing lysosomes, highlighting its potential as a therapeutic agent against nanoplastics-exacerbated OA.
