title: The protective effects of Donepezil (DP) against cartilage matrix destruction induced by TNF-α.
abstract: 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-α. 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.
authors.affiliation: Orthopedic Department, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Orthopedic Department, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Electronic address: happyzhou@vip.163.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D000077265:Donepezil; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D007189:Indans / Q000494:pharmacology*; D050856:Interferon Regulatory Factor-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis / Q000235:genetics; D010003:Osteoarthritis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D059748:Proteolysis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D002800:Cholinesterase Inhibitors; D024043:Collagen Type II; D007189:Indans; D050856:Interferon Regulatory Factor-1; D010880:Piperidines; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D014409:Tumor Necrosis Factor-alpha; D000077265:Donepezil; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13
keywords: Collagen type II; Donepezil; MMP-13; Osteoarthritis; TNF-α