title: Excavatolide B Attenuates Rheumatoid Arthritis through the Inhibition of Osteoclastogenesis.
abstract: Osteoclasts are multinucleated giant cells of macrophage/monocyte lineage, and cell differentiation with the upregulation of osteoclast-related proteins is believed to play a major role in the destruction of the joints in the course of rheumatoid arthritis (RA). Pro-inflammatory cytokines, such as interleukin-17A (IL-17A) and macrophage colony-stimulating factor (M-CSF), can be overexpressed in RA and lead to osteoclastogenesis. In a previous study, we found that cultured-type soft coral-derived excavatolide B (Exc-B) exhibited anti-inflammatory properties. In the present study, we thus aimed to evaluate the anti-arthritic activity of Exc-B in in vitro and in vivo models. The results demonstrated that Exc-B inhibits LPS-induced multinucleated cell and actin ring formation, as well as TRAP, MMP-9, and cathepsin K expression. Additionally, Exc-B significantly attenuated the characteristics of RA in adjuvant (AIA) and type II collagen-induced arthritis (CIA) in rats. Moreover, Exc-B improved histopathological features, and reduced the number of TRAP-positive multinucleated cells in the in vivo AIA and CIA models. Immunohistochemical analysis showed that Exc-B attenuated the protein expression of cathepsin K, MMP-2, MMP-9, CD11b, and NFATc1 in ankle tissues of AIA and CIA rats. Level of interleukin-17A and macrophage colony-stimulating factor were also decreased by Exc-B. These findings strongly suggest that Exc-B could be of potential use as a therapeutic agent by inhibiting osteoclast differentiation in arthritis. Moreover, this study also illustrates the use of the anti-inflammatory marine compound, Exc-B, as a potential therapeutic strategy for RA.
authors.affiliation: Department of Marine Biotechnology and Resources, National Sun Yat-sen University, No.70, Lianhai Road, Gushan District, Kaohsiung 80424, Taiwan. chas6119@gmail.com.
authors.forename: Yen-You
authors.initials: YY
authors.lastname: Lin
authors.affiliation: Department of Orthopaedic Surgery, Ping-Tung Christian Hospital, No.60, Dalian Road, Pingtung 90059, Taiwan. jean.tang@msa.hinet.net.
authors.forename: Yen-Hsuan
authors.initials: YH
authors.lastname: Jean
authors.affiliation: Department of Orthopaedic Surgery, Ping-Tung Christian Hospital, No.60, Dalian Road, Pingtung 90059, Taiwan. hplee0929@gmail.com.
authors.forename: Hsin-Pai
authors.initials: HP
authors.lastname: Lee
authors.affiliation: Department of Orthopaedic Surgery, Ping-Tung Christian Hospital, No.60, Dalian Road, Pingtung 90059, Taiwan. linsungchun@yahoo.com.tw.
authors.forename: Sung-Chun
authors.initials: SC
authors.lastname: Lin
authors.affiliation: Department and Graduate Institute of Aquaculture, National Kaohsiung Marine University, No.142, Haizhuan Road, Nanzi District, Kaohsiung 81157, Taiwan. panjade@webmail.nkmu.edu.tw.
authors.forename: Chieh-Yu
authors.initials: CY
authors.lastname: Pan
authors.affiliation: Department of Marine Biotechnology and Resources, National Sun Yat-sen University, No.70, Lianhai Road, Gushan District, Kaohsiung 80424, Taiwan. ma4949@adm.cgmh.org.tw.|Department of Neurosurgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center and Chang Gung University College of Medicine, No.123, Dapi Road, Niaosong District, Kaohsiung 83301, Taiwan. ma4949@adm.cgmh.org.tw.|Department of Neurosurgery, Xiamen Chang Gung Memorial Hospital, No.123, Xiafei Road, Haicang District, Xiamen 361000, China. ma4949@adm.cgmh.org.tw.
authors.forename: Wu-Fu
authors.initials: WF
authors.lastname: Chen
authors.affiliation: Department of Life Science, Institute of Molecular Biology, National Chung-Cheng University, No.168, Sec. 1, University Road, Min-Hsiung, Chia-yi 62102, Taiwan. biosfw@ccu.edu.tw.
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Wu
authors.affiliation: Taiwan Coral Research Center, National Museum of Marine Biology & Aquarium, No.2 Houwan Road, Checheng, Pingtung 94450, Taiwan. x2219@nmmba.gov.tw.|Graduate Institute of Marine Biotechnology, National Dong Hwa University, No.2 Houwan Road, Checheng, Pingtung 94450, Taiwan. x2219@nmmba.gov.tw.
authors.forename: Jui-Hsin
authors.initials: JH
authors.lastname: Su
authors.affiliation: Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, No.386, Dazhong 1st Road, Zuoying District, Kaohsiung 81362, Taiwan. khtsui60@gmail.com.|Department of Obstetrics and Gynecology and Institute of Clinical Medicine, National Yang-Ming University, No.155, Sec. 2, Linong Street, Taipei 11221, Taiwan. khtsui60@gmail.com.|Department of Pharmacy and Graduate Institute of Pharmaceutical Technology, Tajen University, No.20, Weixin Road, Yanpu, Pingtung 90741, Taiwan. khtsui60@gmail.com.
authors.forename: Kuan-Hao
authors.initials: KH
authors.lastname: Tsui
authors.affiliation: Department of Marine Biotechnology and Resources, National Sun Yat-sen University, No.70, Lianhai Road, Gushan District, Kaohsiung 80424, Taiwan. sheu@mail.nsysu.edu.tw.|Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, No.70, Lianhai Road, Gushan District, Kaohsiung 80424, Taiwan. sheu@mail.nsysu.edu.tw.
authors.forename: Jyh-Horng
authors.initials: JH
authors.lastname: Sheu
authors.affiliation: Taiwan Coral Research Center, National Museum of Marine Biology & Aquarium, No.2 Houwan Road, Checheng, Pingtung 94450, Taiwan. pjsung@nmmba.gov.tw.|Graduate Institute of Marine Biotechnology, National Dong Hwa University, No.2 Houwan Road, Checheng, Pingtung 94450, Taiwan. pjsung@nmmba.gov.tw.
authors.forename: Ping-Jyun
authors.initials: PJ
authors.lastname: Sung
authors.affiliation: Department of Marine Biotechnology and Resources, National Sun Yat-sen University, No.70, Lianhai Road, Gushan District, Kaohsiung 80424, Taiwan. wzh@mail.nsysu.edu.tw.|Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, No.70, Lianhai Road, Gushan District, Kaohsiung 80424, Taiwan. wzh@mail.nsysu.edu.tw.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Wen
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D056657:Cathepsin K / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D020381:Interleukin-17 / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D053245:RANK Ligand / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D039481:CD11b Antigen; D016207:Cytokines; D004224:Diterpenes; D020381:Interleukin-17; D050778:NFATC Transcription Factors; D053245:RANK Ligand; C574336:excavatolide B; D016173:Macrophage Colony-Stimulating Factor; D056657:Cathepsin K; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: (Exc-B); excavatolide B; osteoclast; osteoclastogenesis; rheumatoid arthritis (RA)