Abstract

Background As a chronic joint disease, osteoarthritis (OA) severely impairs patients’ quality of life and mobility. The deubiquitinating enzyme USP14 and Cadherin-11 (CDH11) have been implicated in OA pathogenesis. However, the regulatory interplay between them remains poorly defined. Methods IL-1β was used to stimulate chondrocytes for in vitro OA model establishment. Bioinformatics database was employed to assess CDH11 expression in OA samples. MTT assay was performed to evaluate cell viability. Protein expression was analyzed via Western blot. Cell apoptosis was detected by flow cytometry. Levels of ROS, GSH, MDA, Fe 2+ , as well as concentrations of TNF-α and IL-6, were measured using respective assay kits. Results CDH11 expression was upregulated in OA samples and IL-1β-induced chondrocytes. Moreover, silencing CDH11 promoted cell viability and attenuated cell apoptosis, inflammation, oxidative stress, and ferroptosis. USP14 stabilized CDH11 through deubiquitination, sustaining CDH11-mediated chondrocyte damage. After USP14 knockdown, cell viability was increased, while cell apoptosis, inflammation, oxidative stress and ferroptosis were mitigated. Furthermore, CDH11 overexpression abrogated the effects of USP14 knockdown on IL-1β-stimulated chondrocytes. Conclusion USP14 mediates IL-1β-induced chondrocyte injury by stabilizing CDH11 through deubiquitination, highlighting the USP14-CDH11 axis as a potential regulatory pathway in OA-related chondrocyte pathology. Key Points • CDH11 is highly expressed in OA samples and IL-1β-induced chondrocytes.. • Silencing CDH11 inhibits IL-1β-induced cell injury, oxidative stress and ferroptosis, confirming CDH11 as a pro-injury factor for chondrocytes. • USP14 stabilizes CDH11 through deubiquitination. •  Overexpression of CDH11 reverses the effects of USP14 knockdown on IL-1-induced chondrocytes.