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Cirsium japonicum var. maackii and apigenin block Hif-2alpha-induced osteoarthritic cartilage destruction

Authors
Cho, C | Kang, LJ  | Jang, D | Jeon, J | Lee, H | Choi, S | Han, SJ | Oh, E | Nam, J | Kim, CS | Park, E  | Jeong, SY  | Park, CH | Shin, YS | Eyun, SI | Yang, S
Citation
Journal of cellular and molecular medicine, 23(8). : 5369-5379, 2019
Journal Title
Journal of cellular and molecular medicine
ISSN
1582-18381582-4934
Abstract
Although Hif-2alpha is a master regulator of catabolic factor expression in osteoarthritis development, Hif-2alpha inhibitors remain undeveloped. The aim of this study was to determine whether Cirsium japonicum var. maackii (CJM) extract and one of its constituents, apigenin, could attenuate the Hif-2alpha-induced cartilage destruction implicated in osteoarthritis progression. In vitro and in vivo studies demonstrated that CJM reduced the IL-1beta-, IL-6, IL-17- and TNF-alpha-induced up-regulation of MMP3, MMP13, ADAMTS4, ADAMTS5 and COX-2 and blocked osteoarthritis development in a destabilization of the medial meniscus mouse model. Activation of Hif-2alpha, which directly up-regulates MMP3, MMP13, ADAMTS4, IL-6 and COX-2 expression, is inhibited by CJM extract. Although cirsimarin, cirsimaritin and apigenin are components of CJM and can reduce inflammation, only apigenin effectively reduced Hif-2alpha expression and inhibited Hif-2alpha-induced MMP3, MMP13, ADAMTS4, IL-6 and COX-2 expression in articular chondrocytes. IL-1beta induction of JNK phosphorylation and IkappaB degradation, representing a critical pathway for Hif-2alpha expression, was completely blocked by apigenin in a concentration-dependent manner. Collectively, these effects indicate that CJM and one of its most potent constituents, apigenin, can lead to the development of therapeutic agents for blocking osteoarthritis development as novel Hif-2alpha inhibitors.
Keywords
MeSH

DOI
10.1111/jcmm.14418
PMID
31148341
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
Journal Papers > School of Medicine / Graduate School of Medicine > Medical Genetics
Ajou Authors
강, 이중  |  박, 은국  |  양, 시영  |  정, 선용
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