Excavatolide B Attenuates Rheumatoid Arthritis through the Inhibition of Osteoclastogenesis
Yen-You Lin,
Yen-Hsuan Jean,
Hsin-Pai Lee,
Sung-Chun Lin,
Chieh-Yu Pan,
Wu-Fu Chen,
Shu-Fen Wu,
Jui-Hsin Su,
Kuan-Hao Tsui,
Jyh-Horng Sheu,
Ping-Jyun Sung,
Zhi-Hong Wen
Affiliations
Yen-You Lin
Department of Marine Biotechnology and Resources, National Sun Yat-sen University, No.70, Lianhai Road, Gushan District, Kaohsiung 80424, Taiwan
Yen-Hsuan Jean
Department of Orthopaedic Surgery, Ping-Tung Christian Hospital, No.60, Dalian Road, Pingtung 90059, Taiwan
Hsin-Pai Lee
Department of Orthopaedic Surgery, Ping-Tung Christian Hospital, No.60, Dalian Road, Pingtung 90059, Taiwan
Sung-Chun Lin
Department of Orthopaedic Surgery, Ping-Tung Christian Hospital, No.60, Dalian Road, Pingtung 90059, Taiwan
Chieh-Yu Pan
Department and Graduate Institute of Aquaculture, National Kaohsiung Marine University, No.142, Haizhuan Road, Nanzi District, Kaohsiung 81157, Taiwan
Wu-Fu Chen
Department of Marine Biotechnology and Resources, National Sun Yat-sen University, No.70, Lianhai Road, Gushan District, Kaohsiung 80424, Taiwan
Shu-Fen Wu
Department of Life Science, Institute of Molecular Biology, National Chung-Cheng University, No.168, Sec. 1, University Road, Min-Hsiung, Chia-yi 62102, Taiwan
Jui-Hsin Su
Taiwan Coral Research Center, National Museum of Marine Biology & Aquarium, No.2 Houwan Road, Checheng, Pingtung 94450, Taiwan
Kuan-Hao Tsui
Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, No.386, Dazhong 1st Road, Zuoying District, Kaohsiung 81362, Taiwan
Jyh-Horng Sheu
Department of Marine Biotechnology and Resources, National Sun Yat-sen University, No.70, Lianhai Road, Gushan District, Kaohsiung 80424, Taiwan
Ping-Jyun Sung
Taiwan Coral Research Center, National Museum of Marine Biology & Aquarium, No.2 Houwan Road, Checheng, Pingtung 94450, Taiwan
Zhi-Hong Wen
Department of Marine Biotechnology and Resources, National Sun Yat-sen University, No.70, Lianhai Road, Gushan District, Kaohsiung 80424, Taiwan
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.
