title: Chitosan oligosaccharide suppresses synovial inflammation via AMPK activation: An in vitro and in vivo study.
abstract: Synovial inflammation plays an important role in the early pathogenesis of osteoarthritis (OA). Chitosan oligosaccharide (COS) has been shown to activate AMPK and suppress inflammatory responses in intestinal epithelial cells. This study aimed to investigate the effect of COS on AMPK activation and synovial inflammation using both primary cultures of synoviocytes and a rabbit model of anterior cruciate ligament (ACL) transection-induced OA. COS induced AMPK activation in both rabbit and human synoviocytes. The mechanism of COS-induced AMPK activation involves an increase in the ADP/ATP ratio but not calcium/calmodulin-dependent protein kinase kinase beta (CaMKKβ). Interestingly, COS suppressed the TNFα-induced iNOS and COX-2 expression via an AMPK-dependent mechanism in both rabbit and human synoviocytes. Importantly, oral administration of COS (10mg/kg/day) induced AMPK activation and alleviated signs of inflammation including COX-2 expression in the synovium of a rabbit ACL transection model. Taken together, our results indicate that COS suppresses synovial inflammation in vitro and in vivo via AMPK activation. COS may be useful in the prevention of OA.
authors.affiliation: Department of Physiology, Faculty of Science, Mahidol University, Rama VI Road, Rajathevi, Bangkok 10400, Thailand.
authors.forename: Wanlop
authors.initials: W
authors.lastname: Kunanusornchai
authors.affiliation: Department of Orthopedics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Rama VI Road, Rajathevi, Bangkok 10400, Thailand.
authors.forename: Bhee
authors.initials: B
authors.lastname: Witoonpanich
authors.affiliation: Department of Orthopedics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Rama VI Road, Rajathevi, Bangkok 10400, Thailand.
authors.forename: Tulyapruek
authors.initials: T
authors.lastname: Tawonsawatruk
authors.affiliation: Department of Biochemistry, Faculty of Science, Chulalongkorn University, Phayathai Road, Phayathai, Bangkok 10330, Thailand.
authors.forename: Rath
authors.initials: R
authors.lastname: Pichyangkura
authors.affiliation: Department of Physiology, Faculty of Science, Mahidol University, Rama VI Road, Rajathevi, Bangkok 10400, Thailand.
authors.forename: Varanuj
authors.initials: V
authors.lastname: Chatsudthipong
authors.affiliation: Department of Physiology, Faculty of Science, Mahidol University, Rama VI Road, Rajathevi, Bangkok 10400, Thailand; Excellent Center for Drug Discovery (ECDD), Faculty of Science, Mahidol University, Rama VI Road, Rajathevi, Bangkok 10400, Thailand. Electronic address: chatchai.mua@mahidol.ac.th.
authors.forename: Chatchai
authors.initials: C
authors.lastname: Muanprasat
mesh_terms: D000818:Animals; D016118:Anterior Cruciate Ligament / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D048271:Chitosan / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009844:Oligosaccharides / Q000494:pharmacology*; D010003:Osteoarthritis / Q000378:metabolism / Q000517:prevention & control; D011817:Rabbits; D000070918:Synoviocytes / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D009844:Oligosaccharides; D014409:Tumor Necrosis Factor-alpha; D048271:Chitosan; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases
keywords: AMPK; Chitosan oligosaccharide; NF-κB; Osteoarthritis; Synovial fibroblast