Related Experiment Video
Updated: Mar 21, 2026
Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
Disulfidptosis-Induced Chondrocyte-Macrophage Crosstalk via GYS1/CCND1/NOD2 Axis Promotes Osteoarthritis Progression
Qing Sun1, Zhihui Wei1, Gaohai Shao1
1Department of Orthopedics, Affiliated Yongchuan Hospital of Chongqing Medical University, Chongqing, 402160, People's Republic of China.
Purpose:
To investigate the potential role and underlying mechanisms of disulfidptosis, a novel form of regulated cell death, in the pathogenesis of degenerative osteoarthritis (OA), and to evaluate its association with M1-type macrophage infiltration and diagnostic biomarker potential.
Methods:
Human articular cartilage samples from OA patients and non-OA controls were analyzed using high-throughput RNA sequencing to identify disulfidptosis-related gene expression patterns. Immunohistochemical assays were performed to validate key molecular signatures in chondrocytes. Differentially expressed genes (DEGs) were screened to identify candidates linking disulfidptosis to M1 macrophage biology. Functional correlation analyses were conducted to explore gene-immune cell interactions. Glucose starvation was applied to induce disulfidptosis in ATDC5 chondrocyte line; a co-culture system with RAW264.7 macrophage cell line was established to validate their functional roles and underlying mechanisms.
Results:
OA chondrocytes exhibited a low-glucose metabolic state and elevated SLC7A11 (a cystine/glutamate transporter implicated in disulfidptosis) expression, consistent with a disulfidptosis signature, and showed increased immune infiltration of M1-type macrophages. Among the DEGs, Glycogen synthase 1 (GYS1) emerged as a key disulfidptosis-related gene directly regulating transcriptional programs in M1 macrophages. Functional analyses suggested that disulfidptosis in chondrocytes may indirectly promote M1 macrophage-mediated immune infiltration through cyclin D1 (CCND1) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2), thereby contributing to OA progression.
Conclusion:
Disulfidptosis in chondrocytes is associated with M1 macrophage immune infiltration and could drive OA progression. Mechanism genes like GYS1/CCND1/NOD2 have diagnostic potential and could be novel biomarkers and therapeutic targets for OA. These findings highlight the translational potential of targeting disulfidptosis-related pathways to improve OA management and patient outcomes.
Insights
Disulfidptosis, a cell death process, drives osteoarthritis (OA) by promoting M1 macrophage infiltration. Key genes like GYS1 offer potential diagnostic and therapeutic targets for OA treatment.
Area of Science:
- Cell Biology
- Immunology
- Biochemistry
Background:
- Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage breakdown and inflammation.
- Regulated cell death pathways play a crucial role in the pathogenesis of various diseases, including OA.
- Disulfidptosis is a novel form of regulated cell death implicated in cellular stress responses.
Purpose of the Study:
- To investigate the role of disulfidptosis in osteoarthritis pathogenesis.
- To elucidate the mechanisms linking disulfidptosis to M1 macrophage infiltration in OA.
- To evaluate the diagnostic biomarker potential of disulfidptosis-related genes in OA.
Main Methods:
- High-throughput RNA sequencing of human articular cartilage from OA patients and controls.
- Immunohistochemical validation of key molecular signatures in chondrocytes.
- In vitro induction of disulfidptosis in chondrocytes and co-culture with macrophages to study functional interactions.
Main Results:
- OA chondrocytes displayed a disulfidptosis signature, characterized by low-glucose metabolism and elevated SLC7A11 expression.
- Increased M1-type macrophage infiltration was observed in OA cartilage.
- Glycogen synthase 1 (GYS1) was identified as a key disulfidptosis-related gene regulating M1 macrophage transcriptional programs, potentially via CCND1 and NOD2, contributing to OA progression.
Conclusions:
- Disulfidptosis in chondrocytes is linked to M1 macrophage infiltration and contributes to osteoarthritis progression.
- GYS1, CCND1, and NOD2 represent potential diagnostic biomarkers and therapeutic targets for OA.
- Targeting disulfidptosis pathways holds translational potential for improving OA management and patient outcomes.
