title: In vitro anti-osteoclastogenic activity of p38 inhibitor doramapimod via inhibiting migration of pre-osteoclasts and NFATc1 activity.
abstract: The mitogen activated protein kinase p38 plays a role in the receptor activator of NF-ĸB ligand (RANKL)-induced osteoclast differentiation. In this study, we investigated the effect of p38 inhibitor doramapimod on the osteoclast differentiation. Doramapimod significantly inhibited the osteoclastogenesis of bone marrow macrophages (BMMs) via attenuating the activation of p38 induced by M-CSF and RANKL. Importantly, doramapimod blocked the migration and fusion in pre-osteoclasts via the down-regulating NFATc1. The inhibitory effect of doramapimod on the migration/fusion of pre-osteoclasts via inhibiting NFATc1 activity were confirmed by measuring NFATc1 luciferase activity and evaluating the mRNA expression of NFATc1-responsive genes related to the osteoclastic migration/fusion. These results suggested anti-osteoclastogenic activity of doramapimod via inhibiting migration/fusion of pre-osteoclasts and NFATc1 activity.
authors.affiliation: Laboratory of Translational Therapeutics, Pharmacology Research Center, Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea; Department of Biology, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Seong-Hee
authors.initials: SH
authors.lastname: Moon
authors.affiliation: Laboratory of Translational Therapeutics, Pharmacology Research Center, Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea.
authors.forename: Sik-Won
authors.initials: SW
authors.lastname: Choi
authors.affiliation: Laboratory of Translational Therapeutics, Pharmacology Research Center, Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea. Electronic address: hwan@krict.re.kr.
authors.forename: Seong Hwan
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D003864:Depression, Chemical; D015536:Down-Regulation / Q000187:drug effects*; D015870:Gene Expression; D008156:Luciferases / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology; D008264:Macrophages / Q000166:cytology; D008297:Male; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000502:physiology; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D009281:Naphthalenes / Q000494:pharmacology*; D010010:Osteoclasts / Q000166:cytology* / Q000502:physiology*; D011720:Pyrazoles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D010671:Phenylurea Compounds
chemical_list: D008156:Luciferases; D016173:Macrophage Colony-Stimulating Factor; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009281:Naphthalenes; D011720:Pyrazoles; D012333:RNA, Messenger; D048051:p38 Mitogen-Activated Protein Kinases; C494005:Nfatc1 protein, mouse; C452139:doramapimod; D010671:Phenylurea Compounds
keywords: Doramapimod; Fusion; Migration; Osteoclast differentiation; p38 inhibitor