Related Experiment Video
Updated: Jun 12, 2025
Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
Ginkgolide A enhances FoxO1 expression and reduces endoplasmic reticulum stress to mitigate osteoarthritis in mice
Heng Yu1, Jinghao Liang1, Yingying Bao2
1Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
Abstract:
This study aimed to investigate the effects of Ginkgolide A (GA) on chondrocytes under oxidative stress and to elucidate its potential molecular mechanisms. Using a destabilization of the medial meniscus (DMM) model in mice and an in vitro osteoarthritis (OA) model induced by tert-butyl hydroperoxide (TBHP) in chondrocytes, we validated the therapeutic efficacy and underlying mechanisms of GA. Potential OA targets of GA were identified through network pharmacology, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Further exploration into the effects on endoplasmic reticulum stress (ERS), apoptosis, extracellular matrix (ECM) degradation, and Forkhead Box O1 (FoxO1) related pathways was conducted using Western blotting, immunofluorescence, TUNEL staining, flow cytometry, X-ray, micro-computed tomography (Micro-CT) analysis, and histological staining. The results demonstrated that GA upregulated FoxO1 expression and inhibited ERS-related signaling pathways, thereby reducing apoptosis and ECM degradation. In conclusion, GA significantly alleviated OA symptoms both in vitro and in vivo, suggesting its potential as a therapeutic agent for OA.
Insights
Ginkgolide A (GA) effectively treats osteoarthritis (OA) by reducing chondrocyte apoptosis and extracellular matrix degradation. This study reveals GA
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage breakdown.
- Oxidative stress plays a critical role in OA pathogenesis.
- Developing effective therapeutic agents for OA remains a significant challenge.
Purpose of the Study:
- To investigate the therapeutic effects of Ginkgolide A (GA) on chondrocytes under oxidative stress.
- To elucidate the molecular mechanisms underlying GA's action in osteoarthritis.
- To validate GA's efficacy using both in vitro and in vivo osteoarthritis models.
Main Methods:
- Utilized a destabilization of the medial meniscus (DMM) mouse model and tert-butyl hydroperoxide (TBHP)-induced chondrocyte model.
- Employed network pharmacology, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to identify OA targets.
- Assessed endoplasmic reticulum stress (ERS), apoptosis, extracellular matrix (ECM) degradation, and Forkhead Box O1 (FoxO1) pathways via Western blotting, immunofluorescence, TUNEL staining, flow cytometry, and imaging techniques (X-ray, Micro-CT, histology).
Main Results:
- GA upregulated Forkhead Box O1 (FoxO1) expression in chondrocytes.
- GA inhibited endoplasmic reticulum stress (ERS)-related signaling pathways.
- GA significantly reduced chondrocyte apoptosis and extracellular matrix (ECM) degradation, alleviating OA symptoms in vitro and in vivo.
Conclusions:
- Ginkgolide A (GA) demonstrates significant therapeutic potential for osteoarthritis (OA).
- GA alleviates OA by modulating FoxO1 expression and inhibiting ERS, apoptosis, and ECM degradation.
- GA warrants further investigation as a novel therapeutic agent for OA treatment.
