Background Rheumatoid arthritis (RA) is a common rheumatic disease that is characterized by synovial inflammation of the synovial tissue that lines the joints . Osteoclasts become active and mature by stimulation of inflammatory cytokines such as macrophage colony-stimulating factor (M-CSF), interleukin-1b (IL-1b), interleukin-17A (IL-17A), and tumor necrosis factor-a (TNF-a), and also play a critical role in the bone destruction in RA . Soft corals have been considered an important resource of anti-inflammatory agents that may be beneficial for treating inflammatory diseases [3–5].
Objectives In this present study, we investigated the therapeutic effects of CSD-125, a soft coral-derived compound in type II collagen-induced arthritis (CIA), via its role in the anti-osteoclastic pathway.
Methods A rat model of CIA was established, and knee joint tissue destruction was evaluated in rats treated with and without CSD-125 by the RA index, histopathology, immunohistochemistry, and western blotting. We also analyzed the level of pro-inflammatory cytokines such as M-CSF and IL-17A in the blood serum.
Results The results demonstrated that CSD-125 significantly attenuated CIA-induced RA progression in rats. CSD-125 also decreased the expression of osteoclast-related proteins, including cathepsin K, matrix metalloproteinases-9, matrix metalloproteinases-2, cluster of differentiation molecule 11B, nuclear factor of activated T cells, cytoplasmic 1 (NFATC 1), and triggering receptor on myeloid cells 2 (TREM 2), in multinucleated cells. Moreover, CSD-125 reduced the number of cells showing positive expression of IL-17A, IL-1b, and TNF-a, phospho-extracellular signal-regulated kinases (p-ERK), phospho-c-Jun N-terminal kinase (p-JNK), and phospho-p38 (p-P38) in the synovial tissue of CIA-rats. The levels of M-CSF and IL-17A also decreased following administration of CSD-125 to CIA-rats.
Conclusions These results provide strong support that CSD-125 could attenuate the joint destruction in type II CIA, likely through inhibition of osteoclast activation.
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Acknowledgement This study was supported by grants from the Ministry of Science and Technology (MOST 103–2628-B-110–002-MY3 and MOST 104–2325-B-110–001) of Taiwan and Pingtung Christian Hospital, Taiwan.
Disclosure of Interest None declared