Rheumatology (Oxford, England) · 2025
IGFBP5 regulates fibrocartilage differentiation and cartilage injury induced by T-2 toxin via blocking IGF-1/IGF-1R signalling.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Wang Xiaoqing, Wang Yinxia, Lei Pengzhen, Qu Xiaodong, Qi Rui, Chen Duanmingyu, Chang Yanhai
Аннотация
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. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (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 the reduction of CPC function in KBD model.
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. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (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 the reduction of CPC function in KBD model.