Naringin Prevents Bone Damage in the Experimental Metabolic Syndrome Induced by a Fructose Rich Diet

2021 ◽  
Author(s):  
María Rivoira ◽  
Alfredo Rigalli ◽  
Lucía Corball ◽  
Nori Tolosa de Talamoni ◽  
Valeria Rodriguez
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Bone Marrow ◽  
Bone Formation ◽  
Antioxidant Properties ◽  
Biomechanical Properties ◽  
Long Bones ◽  
Mineral Density ◽  
Cortical Bone Mineral Density ◽  
Mean Size

We have analyzed the effect of naringin (NAR), a flavonoid from citric fruits, on bone quality and bone biomechanical properties as well as the redox state of bone marrow in rats fed a fructose rich diet (FRD), an experimental model to mimic human metabolic syndrome. NAR blocked the enhancement in the number of osteoclasts and adipocytes and the decrease in the number of osteocytes and osteocalcin (+) cells caused by FRD. The trabecular number was significantly higher in the FRD+NAR group. FRD induced a decrease in femoral trabecular and cortical bone mineral density, which was blocked by NAR. The fracture and ultimate loads were also decreased by the FRD and FRD+NAR groups. NAR increased the number of nodes to terminal trabecula, the number of nodes to node trabecula, the number of nodes, and the number of nodes with two terminals, and decreased the Dist (mean size of branches) value. Bone marrow catalase activity was decreased by the FRD, an effect prevented by NAR. In conclusion, FRD produces detrimental effects on long bones, which are associated with oxidative stress in bone marrow. Most of these changes are avoided by NAR through its antioxidant properties and promotion of bone formation. Novelty bullets: • Fructose rich diet produces detrimental effects on long bones, which are associated with oxidative stress in bone marrow. • Most of these changes are avoided by Naringin through its antioxidant properties and promotion of bone formation.

scholarly journals Topical co‐administration of zoledronate with recombinant human bone morphogenetic protein-2 can induce and maintain bone formation in the bone marrow environment

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hideki Ueyama ◽  
Yoichi Ohta ◽  
Yuuki Imai ◽  
Akinobu Suzuki ◽  
Ryo Sugama ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Bone Structure ◽  
Precursor Cells ◽  
The Other ◽  
Bone Morphogenetic Protein 2 ◽  
New Bone Formation ◽  
Micro Computed Tomography ◽  
Mineral Density ◽  
Left Femur

Abstract Background Bone morphogenetic proteins (BMPs) induce osteogenesis in various environments. However, when BMPs are used alone in the bone marrow environment, the maintenance of new bone formation is difficult owing to vigorous bone resorption. This is because BMPs stimulate the differentiation of not only osteoblast precursor cells but also osteoclast precursor cells. The present study aimed to induce and maintain new bone formation using the topical co-administration of recombinant human BMP-2 (rh-BMP-2) and zoledronate (ZOL) on beta-tricalcium phosphate (β-TCP) composite. Methods β-TCP columns were impregnated with both rh-BMP-2 (30 µg) and ZOL (5 µg), rh-BMP-2 alone, or ZOL alone, and implanted into the left femur canal of New Zealand white rabbits (n = 56). The implanted β-TCP columns were harvested and evaluated at 3 and 6 weeks after implantation. These harvested β-TCP columns were evaluated radiologically using plane radiograph, and histologically using haematoxylin/eosin (H&E) and Masson’s trichrome (MT) staining. In addition, micro-computed tomography (CT) was performed for qualitative analysis of bone formation in each group (n = 7). Results Tissue sections stained with H&E and MT dyes revealed that new bone formation inside the β-TCP composite was significantly greater in those impregnated with both rh-BMP-2 and ZOL than in those from the other experimental groups at 3 and 6 weeks after implantations (p < 0.05). Micro-CT data also demonstrated that the bone volume and the bone mineral density inside the β-TCP columns were significantly greater in those impregnated with both rh-BMP-2 and ZOL than in those from the other experimental groups at 3 and 6 weeks after implantations (p < 0.05). Conclusions The topical co-administration of both rh-BMP-2 and ZOL on β-TCP composite promoted and maintained newly formed bone structure in the bone marrow environment.

scholarly journals Effects of Nrf2 Deficiency on Bone Microarchitecture in an Experimental Model of Osteoporosis

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Lidia Ibáñez ◽  
María Luisa Ferrándiz ◽  
Rita Brines ◽  
David Guede ◽  
Antonio Cuadrado ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bone Marrow ◽  
Bone Metabolism ◽  
Bone Microarchitecture ◽  
Related Factor ◽  
Mineral Density ◽  
Trabecular Bone Mineral Density ◽  
Bone Marrow Derived Cells

Objective. Redox imbalance contributes to bone fragility. We have evaluated the in vivo role of nuclear factor erythroid derived 2-related factor-2 (Nrf2), an important regulator of cellular responses to oxidative stress, in bone metabolism using a model of postmenopausal osteoporosis.Methods. Ovariectomy was performed in both wild-type and mice deficient in Nrf2 (Nrf2−/−). Bone microarchitecture was analyzed byμCT. Serum markers of bone metabolism were also measured. Reactive oxygen species production was determined using dihydrorhodamine 123.Results. Sham-operated or ovariectomized Nrf2−/−mice exhibit a loss in trabecular bone mineral density in femur, accompanied by a reduction in cortical area in vertebrae. Nrf2 deficiency tended to increase osteoblastic markers and significantly enhanced osteoclastic markers in sham-operated animals indicating an increased bone turnover with a main effect on bone resorption. We have also shown an increased production of oxidative stress in bone marrow-derived cells from sham-operated or ovariectomized Nrf2−/−mice and a higher responsiveness of bone marrow-derived cells to osteoclastogenic stimuli in vitro.Conclusion. We have demonstrated in vivo a key role of Nrf2 in the maintenance of bone microarchitecture.

scholarly journals Ephrin B1 Regulates Bone Marrow Stromal Cell Differentiation and Bone Formation by Influencing TAZ Transactivation via Complex Formation with NHERF1

2009 ◽  
Vol 30 (3) ◽  
pp. 711-721 ◽  
Author(s):  
Weirong Xing ◽  
Jonghyun Kim ◽  
Jon Wergedal ◽  
Shin-Tai Chen ◽  
Subburaman Mohan
Keyword(s):  
Bone Marrow ◽  
Cell Differentiation ◽  
Bone Formation ◽  
Molecular Mechanism ◽  
Osteoblast Differentiation ◽  
Fold Increase ◽  
Mineral Density ◽  
Reverse Signaling ◽  
Calvarial Defects

ABSTRACT Mutations of ephrin B1 in humans result in craniofrontonasal syndrome. Because little is known of the role and mechanism of action of ephrin B1 in bone, we examined the function of osteoblast-produced ephrin B1 in vivo and identified the molecular mechanism by which ephrin B1 reverse signaling regulates bone formation. Targeted deletion of the ephrin B1 gene in type 1α2 collagen-producing cells resulted in severe calvarial defects, decreased bone size, bone mineral density, and trabecular bone volume, caused by impairment in osterix expression and osteoblast differentiation. Coimmunoprecipitation of the TAZ complex with TAZ-specific antibody revealed a protein complex containing ephrin B1, PTPN13, NHERF1, and TAZ in bone marrow stromal (BMS) cells. Activation of ephrin B1 reverse signaling with soluble EphB2-Fc led to a time-dependent increase in TAZ dephosphorylation and shuttling from cytoplasm to nucleus. Treatment of BMS cells with exogenous EphB2-Fc resulted in a 4-fold increase in osterix expression as determined by Western blotting. Disruption of TAZ expression using specific lentivirus small hairpin RNA (shRNA) decreased TAZ mRNA by 80% and ephrin B1 reverse signaling-mediated increases in osterix mRNA by 75%. Knockdown of NHERF1 expression reduced basal levels of osterix expression by 90% and abolished ephrin B1-mediated induction of osterix expression. We conclude that locally produced ephrin B1 mediates its effects on osteoblast differentiation by a novel molecular mechanism in which activation of reverse signaling leads to dephosphorylation of TAZ and subsequent release of TAZ from the ephrin B1/NHERF1/TAZ complex to translocate to the nucleus to induce expression of the osterix gene and perhaps other osteoblast differentiation genes. Our findings provide strong evidence that ephrin B1 reverse signaling in osteoblasts is critical for BMS cell differentiation and bone formation.

scholarly journals Melatonin Ameliorates Autophagy Impairment in a Metabolic Syndrome Model

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 796
Author(s):  
Adrián Santos-Ledo ◽  
Beatriz de Luxán-Delgado ◽  
Beatriz Caballero ◽  
Yaiza Potes ◽  
Susana Rodríguez-González ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Metabolic Diseases ◽  
Antioxidant Properties ◽  
Blood Lipid ◽  
Harderian Gland ◽  
Chow Diet ◽  
Melatonin Treatment ◽  
The Metabolic Syndrome ◽  
Metabolic Syndrome Model

Metabolic syndrome is a global health problem in adults and its prevalence among children and adolescents is rising. It is strongly linked to a lifestyle with high-caloric food, which causes obesity and lipid metabolism anomalies. Molecular damage due to excessive oxidative stress plays a major role during the development of metabolic syndrome complications. Among the different hormones, melatonin presents strong antioxidant properties, and it is used to treat metabolic diseases. However, there is not a consensus about its use as a metabolic syndrome treatment. The aim of this study was to identify melatonin effects in a metabolic syndrome model. Golden hamsters were fed with 60% fructose-enriched food to induce metabolic syndrome and were compared to hamsters fed with regular chow diet. Both groups were also treated with melatonin. Fructose-fed hamsters showed altered blood lipid levels (increased cholesterol and LDL) and phenotypes restored with the melatonin treatment. The Harderian gland (HG), which is an ideal model to study autophagy modulation through oxidative stress, was the organ that was most affected by a fructose diet. Redox balance was altered in fructose-fed HG, inducing autophagic activation. However, since LC3-II was not increased, the impairment must be in the last steps of autophagy. Lipophagy HG markers were also disturbed, contributing to the dyslipidemia. Melatonin treatment improved possible oxidative homeostasis through autophagic induction. All these results point to melatonin as a possible treatment of the metabolic syndrome.

scholarly journals Antiosteoporotic Activity ofDioscorea alataL. cv. Phyto through Driving Mesenchymal Stem Cells Differentiation for Bone Formation

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Kang-Yung Peng ◽  
Lin-Yea Horng ◽  
Hui-Ching Sung ◽  
Hui-Chuan Huang ◽  
Rong-Tsun Wu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Bone Formation ◽  
Trabecular Bone ◽  
Nodule Formation ◽  
Mineral Density ◽  
Osteoporosis Therapy ◽  
Trabecular Bone Mineral Density ◽  
Bone Nodule ◽  
Bone Nodule Formation

The aim of this study was to evaluate the effect of an ethanol extract of the rhizomes ofDioscorea alataL. cv. Phyto, Dispo85E, on bone formation and to investigate the mechanisms involved. Our results showed that Dispo85E increased the activity of alkaline phosphatase (ALP) and bone nodule formation in primary bone marrow cultures. In addition, Dispo85E stimulated pluripotent C3H10T1/2 stem cells to differentiate into osteoblasts rather than adipocytes. Ourin vivodata indicated that Dispo85E promotes osteoblastogenesis by increasing ALP activity and bone nodule formation in both intact and ovariectomized (OVX) mice. Microcomputed tomography (μCT) analysis also showed that Dispo85E ameliorates the deterioration of trabecular bone mineral density (tBMD), trabecular bone volume/total volume (BV/TV), and trabecular bone number (Tb.N) in OVX mice. Our results suggested that Dispo85E is a botanical drug with a novel mechanism that drives the lineage-specific differentiation of bone marrow stromal cells and is a candidate drug for osteoporosis therapy.

scholarly journals Impact of metabolic syndrome and its components on bone remodeling in adolescents

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0253892
Author(s):  
Valéria Nóbrega da Silva ◽  
Tamara Beres Lederer Goldberg ◽  
Carla Cristiane Silva ◽  
Cilmery Suemi Kurokawa ◽  
Luciana Nunes Mosca Fiorelli ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Metabolic Syndrome ◽  
Bone Formation ◽  
Bone Mineral ◽  
Biochemical Markers ◽  
Excess Weight ◽  
Mineral Density ◽  
Biochemical Tests ◽  
The Impact ◽  
Markers Of Bone Formation

Introduction Osteoporosis and metabolic syndrome (MetS) are diseases that have serious public health consequences, reducing the quality of life of patients and increasing morbidity and mortality, with substantial healthcare expenditures. Objective To evaluate the impact of MetS on bone mineral density (BMD) and biochemical markers of bone formation and resorption in adolescents with excess weight. Method A descriptive and analytical cross-sectional study was performed that evaluated 271 adolescents of both sexes (10 to 16 years). From the total sample, 42 adolescents with excess weight and the presence of MetS (14%) were selected. A further 42 adolescents with excess weight and without MetS were chosen, matched for chronological age, bone age, and pubertal developmental criteria to those with MetS, for each sex. Anthropometric measurements, blood pressure collection, and biochemical tests were performed in all adolescents, as well as evaluation of BMD and the bone biomarkers osteocalcin (OC), bone alkaline phosphatase (BAP), and carboxy-terminal telopeptide (S-CTx). Results The adolescents with excess weight and MetS exhibited significantly lower transformed BMD and concentrations of BAP, OC, and S-CTx compared to the matched group, except for OC in boys. A negative and significant correlation was observed between total body BMD and BAP (r = -0.55568; p = 0.005), OC (r = -0.81760; p = < .000), and S-CTx (r = -0.53838; p = 0.011) in girls. Conclusion Metabolic syndrome may be associated with reduced bone mineral density and biochemical markers of bone formation and resorption in adolescents with excess weight.

Oxidative Stress Reducing Osteogenesis Reversed by Curcumin via NF-κB Signaling and Had a Role in Anti-Osteoporosis

2021 ◽  
Author(s):  
Xu JiaQiang ◽  
Ran Gao ◽  
Wen Liang ◽  
ChangJian Wu ◽  
FangLing Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Cell Model ◽  
Antioxidant Properties ◽  
Calcium Content ◽  
Dependent Manner ◽  
Osteoporosis Prevention ◽  
High Concentration ◽  
Mineral Density

Abstract Objective: Curcumin has good anti-inflammatory and antioxidant properties, and whether it can resist osteoporosis through oxidative stress pathway in a dose-dependent manner.Method: we used an oxidative stress cell model by culture cells with hydrogen peroxide (H2O2), cells were osteogenic differentiation after treated with H2O2，different concentration curcumin were added during differentiation, then measured the early and late osteogenic index, and detected the potential signaling pathway involved. In addition, we employed rat OVX model treated with curcumin to confirm the protection of the anti-oxidant.Result: Low concentrations of curcumin (1-10μM) promoted the proliferation of MC3T3-E1 cells, improved alkaline phosphatase (ALP) activity, elevated calcium content against oxidative stress induced by H2O2, but high concentration (20 μM) failed, moreover, curcumin diminished supernatant receptor activator of nuclear factor kappa-B ligand (RANKL) and IL-6 expression, inhibited the intracellular ROS triggered by H2O2, Notably, curcumin exerted protection by blocking the NF-κB signaling pathway. The curcumin administered for 12 weeks partially reversed the raito of blood malondialdehyde (MDA) and glutathione (GSH) activity in ovariectomized (OVX) rat in vivo. It also increased the bone mineral density (BMD) and improved the micro-architecture of trabecular bones. Conclusion: curcumin exerted protection on osteoporosis, the effect linked to a reduction of oxidative stress and bone resorbing cytokine, This study suggests that curcumin might be a candidate for osteoporosis prevention and the low concentration exerted obviously protection.

scholarly journals The Metabolic Syndrome, Oxidative Stress, Environment, and Cardiovascular Disease: The Great Exploration

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Rebecca Hutcheson ◽  
Petra Rocic
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Angiotensin Ii ◽  
Coronary Revascularization ◽  
Antioxidant Properties ◽  
Type I ◽  
Apparent Lack ◽  
The Metabolic Syndrome ◽  
The Impact

The metabolic syndrome affects 30% of the US population with increasing prevalence. In this paper, we explore the relationship between the metabolic syndrome and the incidence and severity of cardiovascular disease in general and coronary artery disease (CAD) in particular. Furthermore, we look at the impact of metabolic syndrome on outcomes of coronary revascularization therapies including CABG, PTCA, and coronary collateral development. We also examine the association between the metabolic syndrome and its individual component pathologies and oxidative stress. Related, we explore the interaction between the main external sources of oxidative stress, cigarette smoke and air pollution, and metabolic syndrome and the effect of this interaction on CAD. We discuss the apparent lack of positive effect of antioxidants on cardiovascular outcomes in large clinical trials with emphasis on some of the limitations of these trials. Finally, we present evidence for successful use of antioxidant properties of pharmacological agents, including metformin, statins, angiotensin II type I receptor blockers (ARBs), and angiotensin II converting enzyme (ACE) inhibitors, for prevention and treatment of the cardiovascular complications of the metabolic syndrome.

Estrogen-induced osteogenesis in intact female mice lacking ERβ

2002 ◽  
Vol 283 (4) ◽  
pp. E817-E823 ◽  
Author(s):  
K. E. McDougall ◽  
M. J. Perry ◽  
R. L. Gibson ◽  
J. M. Bright ◽  
S. M. Colley ◽  
...  
Keyword(s):  
Bone Formation ◽  
Cancellous Bone ◽  
Cross Sections ◽  
Mineral Apposition Rate ◽  
High Dose ◽  
Long Bones ◽  
Mineral Density ◽  
Intact Female ◽  
Targeted Gene Deletion ◽  
Osteogenic Response

We recently found that estrogen receptor (ER) antagonists prevent high-dose estrogen from inducing the formation of new cancellous bone within the medullary cavity of mouse long bones. In the present investigation, we studied the role of specific ER subtypes in this response by examining whether this is impaired in female ERβ−/− mice previously generated by targeted gene deletion. Vehicle or 17β-estradiol (E2) (range 4–4,000 μg · kg−1 · day−1) was administered to intact female ERβ−/− mice and wild-type littermates by subcutaneous injection for 28 days. The osteogenic response was subsequently assessed by histomorphometry performed on longitudinal and cross sections of the tibia. E2 was found to cause an equivalent increase in cancellous bone formation in ERβ−/− mice and littermate controls, as assessed at the proximal and distal regions of the proximal tibial metaphysis. E2 also resulted in a similar increase in endosteal mineral apposition rate in these two genotypes, as assessed at the tibial diaphysis. In contrast, cortical area in ERβ−/− mice was found to be greater than that in wild types irrespective of E2 treatment, as was tibial bone mineral density as measured by dual-energy X-ray absorptiometry, consistent with previous reports of increased cortical bone mass in these animals. We conclude that, although ERβ acts as a negative modulator of cortical modeling, this isoform does not appear to contribute to high-dose estrogen's ability to induce new cancellous bone formation in mouse long bones.

scholarly journals The Lyme Disease Pathogen Borrelia burgdorferi Infects Murine Bone and Induces Trabecular Bone Loss

2016 ◽  
Vol 85 (2) ◽  
Author(s):  
Tian Tian Tang ◽  
Lucia Zhang ◽  
Anil Bansal ◽  
Marc Grynpas ◽  
Tara J. Moriarty
Keyword(s):  
Lyme Disease ◽  
Bone Loss ◽  
Borrelia Burgdorferi ◽  
Trabecular Bone ◽  
Copy Number ◽  
Bone Microarchitecture ◽  
Biomechanical Properties ◽  
Long Bones ◽  
Mineral Density ◽  
Content Type

ABSTRACT Lyme disease is caused by members of the Borrelia burgdorferi sensu lato species complex. Arthritis is a well-known late-stage pathology of Lyme disease, but the effects of B. burgdorferi infection on bone at sites other than articular surfaces are largely unknown. In this study, we investigated whether B. burgdorferi infection affects bone health in mice. In mice inoculated with B. burgdorferi or vehicle (mock infection), we measured the presence of B. burgdorferi DNA in bones, bone mineral density (BMD), bone formation rates, biomechanical properties, cellular composition, and two- and three-dimensional features of bone microarchitecture. B. burgdorferi DNA was detected in bone. In the long bones, increasing B. burgdorferi DNA copy number correlated with reductions in areal and trabecular volumetric BMDs. Trabecular regions of femora exhibited significant, copy number-correlated microarchitectural disruption, but BMD, microarchitectural, and biomechanical properties of cortical bone were not affected. Bone loss in tibiae was not due to increased osteoclast numbers or bone-resorbing surface area, but it was associated with reduced osteoblast numbers, implying that bone loss in long bones was due to impaired bone building. Osteoid-producing and mineralization activities of existing osteoblasts were unaffected by infection. Therefore, deterioration of trabecular bone was not dependent on inhibition of osteoblast function but was more likely caused by blockade of osteoblastogenesis, reduced osteoblast survival, and/or induction of osteoblast death. Together, these data represent the first evidence that B. burgdorferi infection induces bone loss in mice and suggest that this phenotype results from inhibition of bone building rather than increased bone resorption.

Sign in / Sign up

Export Citation Format

Share Document