IGFBP5 regulates fibrocartilage differentiation and cartilage injury induced by T-2 toxin via blocking IGF-1/IGF-1R signaling

IF 4.7 2区医学 Q1 RHEUMATOLOGY

Rheumatology Pub Date : 2025-02-11 DOI:10.1093/rheumatology/keaf084

Xiaoqing Wang, Yinxia Wang, Pengzhen Lei, Xiaodong Qu, Rui Qi, Duanmingyu Chen, Yanhai Chang

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引用次数: 0

Abstract

Objectives Kashin-Beck disease (KBD) is a form of osteoarthropathy that affects the skeletal and joint systems of children and adolescents. Insulin-like Growth Factor Binding Protein 5 (IGFBP5) plays an important role in bone growth and development. This study aimed to investigate the role of IGBFP5 in regulating the function and differentiation of chondrocytes in KBD. Methods The mRNA and protein expressions of IGFBP5, IGF-1 and IGF-1R were detected by RT-qPCR and western blot assays. Commercial kits were performed to measure the mitochondrial ROS content, calcium loading and ATP synthesis in chondrocytes. MTT assay was used to detect the cell viability of chondrocytes. Co-IP and pull-down assays were conducted to verify the binding activity of IGFBP5 to IGF-1R. The rat KBD model was constructed by a low selenium diet and T-2 toxin. Results The expression of IGFBP5 was upregulated in KBD patient and rat tissues. Further studies showed that interfering with IGFBP5 effectively inhibited T-2-induced chondrocyte damage and mitochondrial stress. IGFBP5 depressed the interaction between IGF-1 and IGF-1R, thereby affecting the regulation of IGF-1/IGF-1R signalling in the repair of chondrocytes. In addition, the fibrous differentiation of cartilage progenitor cells (CPCs) and the activity and migration of CPCs induced by T-2 stimulation were suppressed under IGFBP5 silence treatment. Conclusion IGFBP5 was upregulated during the pathological progression of KBD, and IGFBP5 competitively bound with IGF-1R to impede the interactions between IGF-1 and IGF-1R. Knockdown of IGFBP5 inhibited fibrotic differentiation and ameliorated reduction of CPC function in KBD model.

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来源期刊

Rheumatology 医学-风湿病学

CiteScore

9.40

自引率

7.30%

发文量

1091

审稿时长

2 months

期刊介绍： Rheumatology strives to support research and discovery by publishing the highest quality original scientific papers with a focus on basic, clinical and translational research. The journal’s subject areas cover a wide range of paediatric and adult rheumatological conditions from an international perspective. It is an official journal of the British Society for Rheumatology, published by Oxford University Press. Rheumatology publishes original articles, reviews, editorials, guidelines, concise reports, meta-analyses, original case reports, clinical vignettes, letters and matters arising from published material. The journal takes pride in serving the global rheumatology community, with a focus on high societal impact in the form of podcasts, videos and extended social media presence, and utilizing metrics such as Altmetric. Keep up to date by following the journal on Twitter @RheumJnl.