title: Elevation of IGFBP2 contributes to mycotoxin T-2-induced chondrocyte injury and metabolism.
abstract: Kashin-Beck disease (KBD) is an endemic degenerative osteoarthropathy. The mycotoxin of T-2 toxin is extensively accepted as a major etiological contributor to KBD. However, its function and mechanism in KBD remains unclearly elucidated. Here, T-2 toxin treatment induced chondrocyte injury in a time- and dose-dependent manner by repressing cell viability and promoting cell necrosis and apoptosis. Importantly, T-2 suppressed the transcription of type II collagen and aggrecan, as well as the release of sulphated glycosaminoglycan (sGAG). Furthermore, exposure to T-2 enhanced the transcription of matrix metalloproteinases (MMPs), including MMP-1, -2, -3 and -9. In contrast to control groups, higher expression of insulin-like growth factor binding protein 2 (IGFBP2) was observed in chondrocytes from KBD patients. Interestingly, T-2 toxin caused a dramatical elevation of IGFBP2 expression in chondrocytes. Mechanism analysis corroborated that cessation of IGFBP2 expression alleviated T-2-induced damage to chondrocytes. Simultaneously, transfection with IGFBP2 siRNA also attenuated matrix synthesis and catabolism-related gene expressions of MMPs. Together, this study validated that T-2 toxin exposure might promote the progression of KBD by inducing chondrocyte injury, suppressing matrix synthesis and accelerating cellular catabolism through IGFBP2. Therefore, this research will elucidate a new insight about how T-2 toxin participate in the pathogenesis of KBD.
authors.affiliation: Department of Orthopaedics, The Third Affiliated Hospital (Shaanxi Provincial People's Hospital), Health Science Center of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, The Third Affiliated Hospital (Shaanxi Provincial People's Hospital), Health Science Center of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, The Third Affiliated Hospital (Shaanxi Provincial People's Hospital), Health Science Center of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Yanhai
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Orthopaedics, The Third Affiliated Hospital (Shaanxi Provincial People's Hospital), Health Science Center of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Dapeng
authors.initials: D
authors.lastname: Duan
authors.affiliation: Department of Orthopaedics, The Third Affiliated Hospital (Shaanxi Provincial People's Hospital), Health Science Center of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Zhengming
authors.initials: Z
authors.lastname: Sun
authors.affiliation: School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, Ministry of Health, 76 West Yanta Road, Xi'an, Shaanxi 710061, PR China. Electronic address: xiongguoxa@163.com.
authors.forename: Xiong
authors.initials: X
authors.lastname: Guo
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013605:T-2 Toxin / Q000008:administration & dosage / Q000633:toxicity*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D018971:Insulin-Like Growth Factor Binding Protein 2; D013605:T-2 Toxin
keywords: Chondrocyte injury; Chondrocyte metabolism; IGFBP2; Kashin-Beck disease; Mycotoxin T-2