Knockdown of KIAA1199 suppresses IL-1β-induced cartilage degradation and inflammatory responses in human chondrocytes through the Wnt/β-catenin signalling pathway
| Autor: | Xiang-hua Wang, Yi-ying Qi, Xiu-mao Li, Xiao-wei Ji, Wei-Ping Chen, Qianhai Ding |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cartilage Articular Male Immunology Interleukin-1beta Hyaluronoglucosaminidase Extracellular matrix Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Chondrocytes Downregulation and upregulation Osteoarthritis medicine Immunology and Allergy Animals Humans Wnt Signaling Pathway Aggrecan Cells Cultured Pharmacology Thrombospondin Gene knockdown Chemistry Cartilage Proteolytic enzymes Wnt signaling pathway Cell biology Up-Regulation 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Gene Knockdown Techniques |
| Zdroj: | International immunopharmacology. 73 |
| ISSN: | 1878-1705 |
| Popis: | The overproduction of proteolytic enzymes and dysregulation of extracellular matrix (ECM) metabolism have been shown to accelerate the degradation process of articular cartilage. The purpose of this study was to investigate the role of KIAA1199 and its association with the pathophysiology of osteoarthritis (OA). We found that the expression of KIAA1199 was significantly upregulated in OA cartilage compared with normal tissues. Serum levels of KIAA1199 were higher in OA patients than in non-OA patients. Furthermore, knockdown of KIAA1199 inhibited interleukin-1 beta (IL-1β)-induced ECM metabolic imbalance by regulating the expression of A disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 5; matrix metallopeptidase-13; aggrecan; and COL2A1. In addition, silencing of KIAA1199 significantly decreased the expression of inflammatory mediators such as prostaglandin E2, IL-6, and TNF-α. Mechanistic analyses further revealed that IL-1β-induced activation of the Wnt/β-catenin pathway was suppressed during KIAA1199 knockdown. Moreover, KIAA1199 expression was also upregulated in an in vivo rat OA model. Together, these results increase our understanding of the emerging role of KIAA1199 in the process of OA degeneration, and may lead to a novel molecular target to prevent cartilage degradation. |
| Databáze: | OpenAIRE |
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