Targeting Caspase-1 in osteoarthritis: multi-omics insights into the effects of VX-765 on human chondrocyte function and phenotype
This study demonstrates that Caspase-1 contributes to OA pathogenesis through both canonical and non-canonical mechanisms, and that VX-765 can alleviate chondrocyte dysfunction. The combined evidence supports VX-765 as a potential disease-modifying target for OA therapy. However, further investigation is warranted to clarify Caspase-1's physiological roles, including possible off-target effects of its inhibitors, in cartilage and other joint tissues and the clinical relevance of inter-individual variability, with genomic variants (e.g., rs61751523) as one potential contributor, for therapeutic application.
Authors
- Penghui Wei (ORCID: https://orcid.org/0000-0003-0920-2779)
- Nicole Schäfer (ORCID: https://orcid.org/0000-0002-3897-624X)
- Susanne Grässel (ORCID: https://orcid.org/0000-0002-2549-8285)
- Zhiheng Kong
- Shushan Li (ORCID: https://orcid.org/0009-0000-1779-6242)
- Marianne Ehrnsperger
- Eva Matalová (ORCID: https://orcid.org/0000-0002-3922-0276)
- Brian H. Johnstone (ORCID: https://orcid.org/0000-0003-2112-3192)
- Jian Mei (ORCID: https://orcid.org/0000-0002-3554-5559)
- Patrick Pann
Institutions
- University of Veterinary Sciences Brno (CZ)
- Fujian Medical University (CN)
- Oregon Health & Science University (US)
- University Hospital Regensburg (DE)
- Czech Academy of Sciences, Institute of Animal Physiology and Genetics (CZ)
- First Affiliated Hospital of Fujian Medical University (CN)
- First Affiliated Hospital of Zhengzhou University (CN)
- Brno University of Technology (CZ)
- University of Regensburg (DE)
Publication Details
- Journal
- Frontiers in Immunology
- Published
- 2025-10-03
- DOI
- https://doi.org/10.3389/fimmu.2025.1677801
- Citations
- 1
- Primary Topic
- Inflammasome and immune disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.81