Related Experiment Video
Updated: Aug 6, 2026
Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
Inhibition of Cathepsin C attenuates osteoarthritis by modulating macrophage activated status and reducing tissue
Ye Tian1, Xinyue Wang1, Xinnan Zhao1
1Department of Anatomy, Dalian Medical University, Dalian, China.
Aims:
Osteoarthritis (OA) is a common degenerative joint disease, with growing evidence suggesting that chronic inflammation plays a critical role in its progression. Targeting chronic inflammation could potentially slow OA development. While Cathepsin C (CatC) has been widely studied in the context of inflammatory diseases, its specific role in OA remains underexplored.
Methods:
To address this question, we used clinical samples of OA patients and a murine OA model to clarify the expression of CatC and its role in OA. By further isolating and culturing OA-related primary cells, we aimed to identify the source of CatC and determine its impact on various cell types. In addition, we used CatC knockdown mice and specific CatC inhibitors AZD7986 to verify the impact of CatC inhibition on OA progress.
Results:
Our results demonstrated that CatC expression was significantly upregulated in OA synovium, with infiltrated macrophages playing a crucial role in this upregulation. Furthermore, CatC was identified as a key factor in promoting the release of inflammatory mediators by facilitating the polarization of macrophages towards pro-inflammatory activation state. In turn, macrophage-derived CatC exacerbated inflammation and cartilage degradation through paracrine effects on synovial fibroblasts and chondrocytes. Knockdown of CatC or administration of the specific CatC inhibitor AZD7986 mitigates cartilage damage and synovial inflammation by reducing the expression of inflammatory factors and matrix-degrading enzymes.
Conclusion:
This study demonstrates that macrophage-derived CatC contributes to OA progression through upregulation of inflammatory mediators and MMP13. These findings suggest that CatC may represent a potential therapeutic target warranting further investigation.
Insights
Cathepsin C (CatC) drives osteoarthritis progression by promoting inflammation and cartilage breakdown via macrophages. Inhibiting CatC significantly reduces OA severity, suggesting it as a potential therapeutic target.
Area of Science:
- Biomedical Research
- Inflammation and Immunology
- Osteoarthritis Pathogenesis
Background:
- Osteoarthritis (OA) is a degenerative joint disease where chronic inflammation is a key driver of progression.
- Cathepsin C (CatC) is implicated in inflammatory diseases, but its role in OA is not well understood.
Purpose of the Study:
- To investigate the expression and function of Cathepsin C (CatC) in osteoarthritis (OA).
- To determine the cellular source and impact of CatC on OA-related cells.
- To evaluate the therapeutic potential of CatC inhibition in OA.
Main Methods:
- Analysis of clinical OA samples and a murine OA model.
- Isolation and culture of OA-associated primary cells.
- CatC knockdown in mice and treatment with the CatC inhibitor AZD7986.
Main Results:
- Cathepsin C (CatC) expression is significantly increased in OA synovium, primarily due to infiltrated macrophages.
- Macrophage-derived CatC promotes pro-inflammatory polarization and exacerbates inflammation and cartilage degradation.
- CatC inhibition (knockdown or AZD7986) reduced cartilage damage and synovial inflammation by decreasing inflammatory factors and MMP13.
Conclusions:
- Macrophage-derived CatC contributes to osteoarthritis progression by upregulating inflammatory mediators and matrix-degrading enzymes like MMP13.
- Cathepsin C (CatC) represents a promising therapeutic target for osteoarthritis treatment.
