coenzyme-q10 and Osteoporosis

Coenzyme Q10 (CoQ10) is a fat‑soluble vitamin‑like substance used for the treatment of a variety of disorders, including osteoporosis. The exact mechanism underlying CoQ10‑mediated protection against osteoporosis remains to be elucidated. The present study aimed to evaluate the effect of CoQ10 on osteoblastic cell proliferation and differentiation, and therapeutic effects on a rat model of osteoporosis. Following treatment with different concentrations of CoQ10, cell proliferation and differentiation of rat bone marrow stromal cells (BMSCs), and expression of osteoblastogenic markers, were measured. Rats with osteoporosis subjected to ovariectomy (OVX) were treated with different concentrations of CoQ10. Serum levels of estrogen and bone metabolism markers were measured. Micro computed tomography scans were used to analyze morphological changes in bones. In addition, mRNA and protein levels of phosphatidylinositol 3,4,5‑trisphosphate 3‑phosphatase and dual‑specificity protein phosphatase PTEN (PTEN)/phosphatidylinositol 4,5‑bisphosphate 3‑kinase (PI3K)/RAC‑alpha serine/threonine‑protein kinase(AKT), were determined. CoQ10 significantly increased the proliferation and osteogenic differentiation of BMSCs in a dose‑dependent manner, with an increased expression of osteogenic markers. CoQ10 significantly decreased bone resorption but exhibited no effect on serum E2 levels in vivo. CoQ10 markedly enhanced bone formation. Furthermore, the abundance of p‑PI3K and p‑AKT increased while PTEN levels decreased in a dose‑dependent manner following administration of CoQ10. CoQ10 stimulates the proliferation and differentiation of BMSCs and is effective for the treatment of OVX‑induced osteoporosis in rats. The above effects of CoQ10 may be mediated by activation of the PTEN/PI3K/AKT pathway.

Topics: Alkaline Phosphatase; Animals; Biomarkers; Bone and Bones; Cell Differentiation; Cell Proliferation; Cell Survival; Female; Mesenchymal Stem Cells; Osteoblasts; Osteogenesis; Osteoporosis; Ovariectomy; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; PTEN Phosphohydrolase; Rats; Ubiquinone; X-Ray Microtomography

During aging, bone mass declines increasing osteoporosis and fracture risks. Oxidative stress has been related to this bone loss, making dietary compounds with antioxidant properties a promising weapon. Male Wistar rats were maintained for 6 or 24 months on diets with fish oil as unique fat source, supplemented or not with coenzyme Q

Topics: Animals; Bone Density; Diet; Dietary Supplements; DNA Damage; Fatty Acids, Omega-3; Femur; Fish Oils; Lipid Peroxidation; Male; Osteoporosis; Oxidative Stress; Rats; Rats, Wistar; Ubiquinone

An age-dependent model of the periodontium was reproduced to evaluate the effect of life-long feeding on a low coenzyme Q10 dosage in n-6, n-3 polyunsaturated fatty acid or monounsaturated fatty acid-based diets on periodontal tissues of young and old rats. Results shown that exacerbated age-related alveolar bone loss previously associated to n-6 polyunsaturated fatty acid diet was attenuated by coenzyme Q10 Gene expression analysis suggests that involved mechanisms might be related to a restored capacity of mitochondria to adapt to aging in gingival cells from rats fed on n-6 polyunsaturated fatty acid. In particular, this could be due to an age-related increase of the rate of mitochondrial biogenesis and a better oxidative and respiratory balance in these animals. From the nutritional and clinical point of view, it is noteworthy that supplementation with coenzyme Q10 could counteract the negative effects of n-6 polyunsaturated fatty acid on alveolar bone loss (a major feature of periodontitis) associated to age.

Topics: Alveolar Bone Loss; Animals; Diet; Disease Models, Animal; Fatty Acids, Omega-6; Male; Osteoporosis; Rats; Rats, Wistar; Ubiquinone; Vitamins

Statins' therapy in osteoporosis can aggravate muscle damage. This study was designed to assess which agent, L-carnitine or coenzyme Q10, could enhance the anti-osteoporotic effect of atorvastatin while antagonizing myopathy in ovariectomized rats.. Forty-eight female Sprague Dawley rats were used; forty rats were ovariectomized while eight were sham-operated. Eight weeks post-ovariectomy, rats were divided into ovariectomized-untreated group and four ovariectomized-treated groups (n=8) which received by gavage (mg/(kg∙d), for 8 weeks) 17β-estradiol (0.1), atorvastatin (50), atorvastatin (50)+L-carnitine (100), or atorvastatin (50)+coenzyme Q10 (20). At the end of therapy, bone mineral density (BMD), bone mineral content (BMC), and serum levels of bone metabolic markers (BMMs) and creatine kinase (CK) were measured. Femurs were used for studying the breaking strength and histopathological changes.. Treatment with atorvastatin+L-carnitine restored BMD, BMC, and bone strength to near normal levels. Estrogen therapy restored BMD and BMC to near normal levels, but failed to increase bone strength. Although atorvastatin and atorvastatin+coenzyme Q10 improved BMD, BMC, and bone strength, they failed to restore levels to normal. All treatments decreased BMMs and improved histopathological changes maximally with atorvastatin+L-carnitine which restored levels to near normal. Atorvastatin aggravated the ovariectomy-induced increase in CK level while estrogen, atorvastatin+L-carnitine, and atorvastatin+coenzyme Q10 decreased its level mainly with atorvastatin+L-carnitine which restored the level to near normal.. Co-administration of L-carnitine, but not coenzyme Q10, enhances the anti-osteoporotic effect of atorvastatin while antagonizing myopathy in ovariectomized rats. This could be valuable in treatment of osteoporotic patients. However, further confirmatory studies are needed.

Topics: Animals; Atorvastatin; Bone Density; Bone Density Conservation Agents; Carnitine; Dose-Response Relationship, Drug; Drug Synergism; Female; Osteoporosis; Ovariectomy; Radiography; Rats; Rats, Sprague-Dawley; Treatment Outcome; Ubiquinone

Spinal cord injury (SCI)‑induced osteoporosis may cause mild trauma to bone and increase the risk of bone fracture. The present study aimed to investigate the efficacy of coenzyme Q (CoQ10) on SCI‑induced osteoporosis in rats. SCI was induced by surgical transection of the cord at the T10‑12 level. Animals were treated with CoQ10 (10 mg/kg; intragastrically) daily from 12 h after the surgery and over 10 subsequent days. At the end of the experimental period, blood was collected from the animals and femurs and tibiae were removed for evaluation using biochemical assays. Treatment with CoQ10 prevented SCI‑induced bone loss by rescuing the decreased levels of bone mineral density and bone mineral content observed in the SCI rats. Furthermore, CoQ10 administration reduced bone malondialdehyde levels with a concomitant increase in superoxide dismutase levels, thus alleviating SCI‑induced oxidative injury. In addition, serum inflammatory cytokine levels were markedly increased in rats post‑SCI, which was attenuated by treatment with CoQ10. Finally, the osteoclast‑specific genes receptor activator of nuclear factor kappa‑B ligand and cathepsin K were significantly upregulated and the osteoblast‑specific gene core‑binding factor alpha 1 in the femur was downregulated following SCI, which was effectively restored following treatment with CoQ10. The results suggested that CoQ10 treatment may be effective in attenuating SCI‑induced osteoporosis.

Topics: Animals; Bone Density Conservation Agents; Drug Evaluation, Preclinical; Femur; Gene Expression; Interleukin-6; Male; Osteoblasts; Osteoclasts; Osteoporosis; Oxidative Stress; Rats, Sprague-Dawley; Spinal Cord Injuries; Tibia; Tumor Necrosis Factor-alpha; Ubiquinone

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.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Marrow Cells; Bone Regeneration; Bone Resorption; CD40 Antigens; Cell Differentiation; Cell Line, Tumor; Core Binding Factor Alpha 1 Subunit; Gene Expression Regulation; Hydrogen Peroxide; I-kappa B Proteins; Isoenzymes; Mice; Monocytes; NF-KappaB Inhibitor alpha; NFATC Transcription Factors; Osteoblasts; Osteoclasts; Osteoporosis; p38 Mitogen-Activated Protein Kinases; RANK Ligand; Reactive Oxygen Species; Signal Transduction; Sp7 Transcription Factor; Tartrate-Resistant Acid Phosphatase; Transcription Factors; Ubiquinone