标题:Cortistatin binds to TNF-α receptors and protects against osteoarthritis
作者:Zhao Y.; Li Y.; Qu R.; Chen X.; Wang W.; Qiu C.; Liu B.; Pan X.;等 更多
作者机构:[Zhao, Y] Department of Orthopedics, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China;[ Li, Y] Department of Orthopedics, Qilu Hospi 更多
通讯作者:Li, W(liweiweizhao@163.com)
通讯作者地址:[Li, W] Department of Pathology, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, China;
来源:EBioMedicine
出版年:2019
卷:41
页码:556-570
DOI:10.1016/j.ebiom.2019.02.035
关键词:Chondrocyte; Cortistatin; NF-κB signaling; Osteoarthritis; TNFR
摘要:Background: Osteoarthritis (OA) is a common degenerative disease, and tumor necrosis factor (TNF-α) is known to play a critical role in OA. Cortistatin (CST) is a neuropeptide discovered over 20 years ago, which plays a vital role in inflammatory reactions. However, it is unknown whether CST is involved in cartilage degeneration and OA development. Methods: The interaction between CST and TNF-α receptors was investigated through Coimmunoprecipitation and Biotin-based solid-phase binding assay. Western blot, Real-time PCR, ELISA, immunofluorescence staining, nitrite production assay and DMMB assay of GAG were performed for the primary chondrocyte experiments. Surgically induced and spontaneous OA models were established and western blot, flow cytometry, Real-time PCR, ELISA, immunohistochemistry and fluorescence in vivo imaging were performed for in vivo experiments. Findings: CST competitively bound to TNFR1 as well as TNFR2. CST suppressed proinflammatory function of TNF-α. Both spontaneous and surgically induced OA models indicated that deficiency of CST led to an accelerated OA-like phenotype, while exogenous CST attenuated OA development in vivo. Additionally, TNFR1- and TNFR2-knockout mice were used for analysis and indicated that TNFRs might be involved in the protective role of CST in OA. CST inhibited activation of the NF-κB signaling pathway in OA. Interpretation: This study provides new insight into the pathogenesis and therapeutic strategy of cartilage degenerative diseases, including OA. Fund: The National Natural Science Foundation of China, the Natural Science Foundation of Shandong Province, Key Research and Development Projects of Shandong Province and the Cross-disciplinary Fund of Shandong University. © 2019 The Authors
收录类别:SCOPUS
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85062076602&doi=10.1016%2fj.ebiom.2019.02.035&partnerID=40&md5=e326696d4a18e9a6b45f7a0dd60ed269
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