Journal
JOURNAL OF ORTHOPAEDIC SURGERY AND RESEARCH
Volume 13, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/s13018-018-0797-y
Keywords
Osteoarthritis; Chondrodyte; Matrix-degrading enzymes; Cartilage anabolism; Brd
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Funding
- National Science Foundation for Distinguished Young Scholars of China [81125013]
- National Natural Science Foundation of China [81472116]
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Background: Proinflammatory cytokines, which can upregulate the expression of matrix- degrading enzymes in chondrocytes, play important roles in the development of osteoarthritis. And a BET protein inhibitor, I-BET151, has been shown to exert an anti-inflammatory effect by repressing the BET protein-mediated expression of inflammatory genes. Our objective is to investigate the effect of I-BET151 on a surgical mouse model of osteoarthritis (OA) and human chondrocytes. Methods: We first treated a surgical mouse model of OA with I-BET151 once per day and evaluated the knee joints at 6 and 8 weeks after treatment. We then pretreated the human chondrocytes with I-BET151 prior to treatment with IL-1 beta or TNF-alpha and checked the expression and activity of the matrix- degrading enzyme genes. We also checked the expression of ACAN, COL2A1, and SOX9. Results: We demonstrated that I-BET151 could prevent articular cartilage damage in the surgical mouse model of OA at an earlier time after treatment, but not at a later time after treatment. I-BET151 could robustly suppress the IL-1 beta- and TNF-alpha-induced expression and activity of several matrix- degrading enzymes in human chondrocytes. I-BET151 could also suppress the expression of ACAN, COL2A1, and SOX9. Conclusions: Our findings suggested that inhibiting BET proteins could exert a repression effect on both of chondrocyte anabolism and catabolism, and the effect of BET protein inhibitor on surgical mouse model of OA needs further evaluation.
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