Work

USP14 promotes osteoarthritis progression by deubiquitinating FZD8 to activate the Wnt/β-catenin signaling pathway

Year: 2025

Type: article

Abstract: Osteoarthritis (OA) is a chronic degenerative disease and associated with multiple pathogenic factors, such as old age, heredity, obesity, mechanical damage and inflammatory gene mutation. In this study, we aimed to explore the functions of ubiquitin specific peptidase 14 (USP14) in OA development. The in vitro model of OA was constructed by stimulating chondrocytes with IL-1β. qRT-PCR and western blot assays were used for gene expression. MTT assay and EdU assay were manipulated to evaluate cell proliferation. Flow cytometry analysis was conducted for cell apoptosis. ELISA kits were utilized to determine the concentrations of inflammatory cytokines. Co-immunoprecipitation (Co-IP) assay and GST pull-down assay were manipulated to estimate the interaction between USP14 and Frizzled 8 (FZD8). Ubiquitination assay was used to evaluate the deubiquitination of FZD8. USP14 was highly expression in OA cartilage tissues and IL-1β-triggered chondrocytes. USP14 silencing aggravated the proliferation and repressed the apoptosis, inflammation and extracellular matrix (ECM) degradation of IL-1β-treated chondrocytes. USP14 could interact with FZD8 and regulate FZD8 expression through FZD8 deubiquitination. Moreover, FZD8 overexpression alleviated the effects of UPS14 silencing on IL-1β-treated chondrocyte proliferation, apoptosis, inflammation and ECM degradation. Additionally, USP14 knockdown inhibited Wnt/β-catenin signal pathway via the deubiquitination of FZD8. USP14 repressed IL-1β-treated chondrocyte proliferation and promoted apoptosis, inflammation and ECM degradation by regulating FZD8 expression and Wnt/β-catenin signal pathway. • USP14 and FZD8 are upregulated in OA cartilage tissues and IL-1β-induced chondrocytes. • USP14 knockdown protects chondrocytes against IL-1β-induced injury. • USP14 stabilizes FZD8 expression by its deubiquitination effect. • USP14 knockdown suppresses IL-1β-induced chondrocytes injury by rgulating FZD8. • USP14/FZD8 activates the Wnt/β-catenin signaling pathway in IL-1β-induced chondrocytes.

Source: Immunobiology

DOI: 10.1016/j.imbio.2025.152905

Authors: Xiaochao Chen, Tiancheng Ma, Yongfeng Chen, Qiang Sun, Huayi Wang, Yuanrui Wang

Institutions: Xijing Hospital, Air Force Medical University

Language: English

Topic: Osteoarthritis Treatment and Mechanisms

Subfield: Rheumatology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,840