期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 35, 期 -, 页码 294-300出版社
ELSEVIER
DOI: 10.1016/j.intimp.2016.03.038
关键词
Iguratimod; Osteoclast; RANKL; Differentiation; Function; Migrations
资金
- National Natural Science Foundation of China (NSFC) [30701129, 30901332, 81172845, 81273294, 81403240, 81401352]
- National Natural Science Foundation of Jiangsu Province [BK2011851, BK2012875, BK20140956, BK20141021]
- special project of clinical medicine from Jiangsu Province [BL2013034]
- Youth Natural Science Foundation of Nanjing University of Chinese Medicine [13XZR12]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Asia Pacific League of Associations for Rheumatology (APLAR)
- International League of Associations for Rheumatology (ILAR)
Introduction: Iguratimod (T-614) has been confirmed as a highly efficacious and safe novel disease-modifying anti-rheumatic drug (DMARD) for rheumatoid arthritis therapy in China and Japan due to its potent anti inflammation effect. Here, we investigate the effects of Iguratimod on osteoclast differentiation, migration and function. Methods: The effect of Iguratimod on osteoclastogenesis, migration and bone resorption were assessed by TRAP staining, transwell migration assay and osteologic discs, respectively. Relative expressions of osteoclastic related genes, chemokines and transcription factors were assessed by reverse transcription polymerase chain reaction (RT-PCR) and signaling pathways were analyzed by western blotting. Results: Iguratimod significantly inhibits osteoclast differentiation, migration and bone resorption in RANKL-induced RAW264.7 cell in a dose-dependent manner. The expressions of osteoclastic related genes including TRAP, CTSK and CTR were increased in RAW264.7 cell upon RANKL stimulation but were obviously suppressed in the presence of Iguratimod. RANKL induced the expression of chemokines including CCL7, CCL4 and CCL12 and osteoclastic related transcription factors of c-Fos, c-Jun and NFATc1 could be significantly inhibited by Iguratimod in a dose dependent manner. Western blotting indicated Iguratimod could suppress the activation of MAPKs and NF-kappa B pathway in RANKL induced osteoclastogenesis in RAW264.7. Conclusions: These findings revealed a directly inhibitory role of Iguratimod on osteoclast formation and function, which is distinct from previous report, suggesting Iguratimod provide a unique therapeutic strategy for RA and especially in light of preventing bone destruction. (C) 2016 Elsevier B.V. All rights reserved.
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