title: Antioxidants, like coenzyme Q10, selenite, and curcumin, inhibited osteoclast differentiation by suppressing reactive oxygen species generation.
abstract: Coenzyme Q10 (CoQ10), selenium, and curcumin are known to be powerful antioxidants. Osteoclasts are capable of resorbing mineralized bone and excessive bone resorption by osteoclasts causes bone loss-related diseases. During osteoclast differentiation, the reactive oxygen species (ROS) acts as a secondary messenger on signal pathways. In this study, we investigated whether antioxidants can inhibit RANKL-induced osteoclastogenesis through suppression of ROS generation and compared the relative inhibitory activities of CoQ10, sodium selenite, and curcumin on osteoclast differentiation. We found that antioxidants markedly inhibited the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells in both bone marrow-derived monocytes (BMMs) and RAW 264.7 cells. Antioxidants scavenged intracellular ROS generation within osteoclast precursors during RANKL-stimulated osteoclastogenesis. These also acted to significantly suppress the gene expression of NFATc1, TRAP, and osteoclast-associated immunoglobulin-like receptor (OSCAR), which are genetic markers of osteoclast differentiation in a dose-dependent manner. These antioxidants also suppressed ROS-induced IκBα signaling pathways for osteoclastogenesis. Specially, curcumin displayed the highest inhibitory effect on osteoclast differentiation when concentrations were held constant. Together, CoQ10, selenite, and curcumin act as inhibitors of RANKL-induced NFATc1 which is a downstream event of NF-κB signal pathway through suppression of ROS generation, thereby suggesting their potential usefulness for the treatment of bone disease associated with excessive bone resorption.
authors.affiliation: Department of Maxillofacial Biomedical Engineering, School of Dentistry and Institute of Oral Biology, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Ho-Jin
authors.initials: HJ
authors.lastname: Moon
authors.forename: Wan-Kyu
authors.initials: WK
authors.lastname: Ko
authors.forename: Song Wook
authors.initials: SW
authors.lastname: Han
authors.forename: Duck-Su
authors.initials: DS
authors.lastname: Kim
authors.forename: Yu-Shik
authors.initials: YS
authors.lastname: Hwang
authors.forename: Hun-Kuk
authors.initials: HK
authors.lastname: Park
authors.forename: Il Keun
authors.initials: IK
authors.lastname: Kwon
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D003474:Curcumin / Q000494:pharmacology*; D015536:Down-Regulation; D015870:Gene Expression / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D053245:RANK Ligand / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D018038:Sodium Selenite / Q000494:pharmacology*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D020672:I-kappa B Proteins; C000606205:Nfkbia protein, mouse; D053245:RANK Ligand; D017382:Reactive Oxygen Species; D014451:Ubiquinone; D000072000:NF-KappaB Inhibitor alpha; C024989:coenzyme Q10; D018038:Sodium Selenite; D003474:Curcumin