期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 454, 期 1, 页码 115-118出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2014.10.046
关键词
Osteoarthritis; Donepezil; TNF-alpha; MMP-13; Collagen type II
资金
- National Natural Science Foundation of China [81271982]
The extracellular matrix apparatuses containing collagen and proteoglycan (aggrecan) are important factors for maintaining the integrity of cartilage. Collagen type II, the main component of total cartilage, is mainly degraded by matrix metalloproteinase13 (MMP-13), which is an important molecule responsible for joint damage in Osteoarthritis (OA). Donepezil (DP), a potent and selective acetylcholinesterase inhibitor, is a medication approved by the US Food and Drug Administration and used in the alleviation of dementia in Alzheimer's disease (AD). In this study, we found that DP treatment prevented the degradation of collagen type II induced by TNF-alpha. Mechanistically, DP treatment leads to the inhibition of the transcriptional activity of interferon response factor-1 (IRF-1), thereby prevents the induction of MMP-13. These findings suggest the potential therapeutic effects of DP in OA. (C) 2014 Elsevier Inc. All rights reserved.
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