Coenzyme Q10 Regulates Osteoclast and Osteoblast Differentiation

• Published in: Journal of food science 2013-05, Vol.78 (5), p.H785-H791
• Main Authors: Moon, Ho-Jin, Ko, Wan-Kyu, Jung, Min-Seo, Kim, Jung Ho, Lee, Won-Jun, Park, Kyoung-Sun, Heo, Ja-Kyung, Bang, Jae Beum, Kwon, Il Keun
• Format: Article
• Language: English
• Subjects: Acid Phosphatase - genetics; Acid Phosphatase - metabolism; Alkaline Phosphatase - genetics; Alkaline Phosphatase - metabolism; Animals; Antioxidants; Biocompatibility; Biological and medical sciences; Biomarkers; Biomedical materials; Bone diseases; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; Bone Regeneration - drug effects; Bone Resorption - drug therapy; Bone Resorption - physiopathology; Bones; CD40 Antigens - genetics; CD40 Antigens - metabolism; Cell Differentiation - drug effects; Cell Line, Tumor; Cells; coenzyme Q10; Core Binding Factor Alpha 1 Subunit - genetics; Core Binding Factor Alpha 1 Subunit - metabolism; Differentiation; Enzymes; Food industries; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Genetic markers; Hydrogen Peroxide - metabolism; I-kappa B Proteins - genetics; I-kappa B Proteins - metabolism; Inhibitors; Isoenzymes - genetics; Isoenzymes - metabolism; IκBα; matrix mineralization; Medical services; Mice; Molecules; Monocytes - cytology; Monocytes - drug effects; Monocytes - metabolism; NF-KappaB Inhibitor alpha; NFATC Transcription Factors - genetics; NFATC Transcription Factors - metabolism; osteoblast; Osteoblasts - drug effects; Osteoblasts - metabolism; osteoclast; Osteoclasts - drug effects; Osteoclasts - metabolism; Osteoporosis - drug therapy; Osteoporosis - physiopathology; p38 Mitogen-Activated Protein Kinases - genetics; p38 Mitogen-Activated Protein Kinases - metabolism; RANK Ligand - genetics; RANK Ligand - metabolism; Reactive Oxygen Species; Receptors; Signal Transduction; Sp7 Transcription Factor; Tartrate-Resistant Acid Phosphatase; Transcription Factors - genetics; Transcription Factors - metabolism; Ubiquinone - analogs & derivatives; Ubiquinone - pharmacology
• ISSN: 0022-1147; 1750-3841
• DOI: 10.1111/1750-3841.12116

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 H2O2‐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. Practical Application  CoQ10 suppresses osteoclast differentiation through H2O2‐induced IκBα, p38 signaling pathways and enhances bone regeneration at all processes of differentiation through Runx2, Osterix activity. CoQ10 may potentially be useful for the treatment of osteoporosis and other bone diseases associated with excessive bone resorption.