title: Coenzyme q10 regulates osteoclast and osteoblast differentiation.
abstract: Coenzyme Q10 (CoQ10), a powerful antioxidant, is a key component in mitochondrial bioenergy transfer, generating energy in the form of ATP. Many studies suggest that antioxidants act as inhibitors of osteoclastogenesis and we also have previously demonstrated the inhibitory effect of CoQ10 on osteoclast differentiation. Despite the significance of this effect, the molecular mechanism when CoQ10 is present at high concentrations in bone remodeling still remains to be elucidated. In this study, we investigated the inhibitory effect of CoQ10 on osteoclastogenesis and its impact on osteoblastogenesis at concentrations ranging from 10 to 100 μM. We found that nontoxic CoQ10 markedly attenuated the formation of receptor activator of nuclear factor κB ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells in both bone-marrow-derived monocytes (BMMs) and RAW 264.7 cells. Osteoclastogenesis with CoQ10 was significantly suppressed the gene expression of NFATc1, TRAP, and osteoclast-associated immunoglobulin-like receptor, which are genetic markers of osteoclast differentiation and scavenged intracellular reactive oxygen species, an osteoclast precursor, in a dose-dependent manner. Furthermore, CoQ10 strongly suppressed H2 O2 -induced IκBα, p38 signaling pathways for osteoclastogenesis. In bone formation study, CoQ10 acted to enhance the induction of osteoblastogenic biomarkers including alkaline phosphatase, type 1 collagen, bone sialoprotein, osteoblast-specific transcription factor Osterix, and Runt-related transcription factor 2 and, also promoted matrix mineralization by enhancing bone nodule formation in a dose-dependent manner. Together, CoQ10 acts as an inhibitor of RANKL-induced osteoclast differentiation and an enhancer of bone-forming osteoblast differentiation. These findings highlight the potential therapeutic applications of CoQ10 for the treatment of bone disease.
authors.affiliation: Dept. of Maxillofacial Biomedical Engineering and Inst. of Oral Biology, School of Dentistry, Kyung Hee Univ., 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: Min-Seo
authors.initials: MS
authors.lastname: Jung
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Won-Jun
authors.initials: WJ
authors.lastname: Lee
authors.forename: Kyoung-Sun
authors.initials: KS
authors.lastname: Park
authors.forename: Ja-Kyung
authors.initials: JK
authors.lastname: Heo
authors.forename: Jae Beum
authors.initials: JB
authors.lastname: Bang
authors.forename: Il Keun
authors.initials: IK
authors.lastname: Kwon
mesh_terms: D000135:Acid Phosphatase / Q000235:genetics / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001861:Bone Regeneration / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy / Q000503:physiopathology; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006861:Hydrogen Peroxide / Q000378:metabolism; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D010024:Osteoporosis / Q000188:drug therapy / Q000503:physiopathology; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D000076182:Sp7 Transcription Factor; D000071681:Tartrate-Resistant Acid Phosphatase; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D019013:CD40 Antigens; D050659:Core Binding Factor Alpha 1 Subunit; D020672:I-kappa B Proteins; D007527:Isoenzymes; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; C000606205:Nfkbia protein, mouse; D053245:RANK Ligand; D017382:Reactive Oxygen Species; C493716:Runx2 protein, mouse; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; D014451:Ubiquinone; D000072000:NF-KappaB Inhibitor alpha; D006861:Hydrogen Peroxide; D048051:p38 Mitogen-Activated Protein Kinases; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; C024989:coenzyme Q10