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Liquiritigenin reduces osteoclast activity in zebrafish model of glucocorticoid-induced osteoporosis


  • 影响因子:2.79
  • DOI:10.1016/j.jphs.2020.06.001
  • 作者列表:"Marta Carnovali","Giuseppe Banfi","Massimo Mariotti
  • 发表时间:2020-06-20

Drug and therapies currently used to treat human bone diseases have a lot of severe side effects. Liquiritigenin is a flavonoid extracted from Glycyrrhiza glabra roots which has been reported to have positive effects in vitro on osteoblasts activity and bone mineralization as well as inhibitory effect on osteoclasts differentiation and activity in vitro. The present study was aimed to evaluate the in vivo effects of liquiritigenin on bone structure and metabolism in physiological and pathological conditions using Danio rerio as experimental animal model. Treatments with liquiritigenin were performed on embryos to evaluate the osteogenesis during skeletal development. Other treatments were performed on adult fish affected by glucocorticoid-induced osteoporosis to assay the therapeutic potential of liquiritigenin in the reversion of bone-loss phenotype in scale model. Liquiritigenin treatment of zebrafish embryo significantly enhances the osteogenesis during development in a dose-dependent manner. In addition, liquiritigenin inhibits the formation of the osteoporotic phenotype in adult zebrafish model of glucocorticoid-induced osteoporosis preventing osteoclast activation in scales. Interestingly, liquiritigenin does not counteract the loss of osteoblastic activity in scales. The liquiritigenin exhibits in vivo anti-osteoporotic activity on adult fish scale model. It can be considered a good candidate to develop new drugs against osteoporosis.


目前用于治疗人类骨骼疾病的药物和疗法有很多严重的副作用。甘草素是从光果甘草根中提取的黄酮类化合物,据报道在体外对成骨细胞活性和骨矿化有积极作用,在体外对破骨细胞分化和活性有抑制作用。本研究旨在以 Danio rerio 为实验动物模型,在体内评价甘草素对生理和病理条件下骨结构和代谢的影响。对胚胎进行甘草素处理,评价骨骼发育过程中的成骨作用。对受糖皮质激素诱导的骨质疏松症影响的成年鱼进行其他治疗,以在尺度模型中测定甘草素在骨丢失表型逆转中的治疗潜力。甘草素处理斑马鱼胚胎可显著增强发育过程中的成骨作用,且呈剂量依赖性。此外,在糖皮质激素诱导的骨质疏松症的成年斑马鱼模型中,甘草素抑制骨质疏松表型的形成,防止破骨细胞在鳞片中活化。有趣的是,甘草素不能抵消鳞屑成骨细胞活性的丧失。甘草素在成年鱼鳞模型上表现出体内抗骨质疏松活性。它可以被认为是开发抗骨质疏松症新药的良好候选药物。



来源期刊:Food & function
作者列表:["Galán MG","Weisstaub A","Zuleta A","Drago SR"]

METHODS::Apparent calcium absorption, total bone mineral content and density, and mineral contents of the right femur were studied using a growing rat model. Twenty-four male Wistar rats were fed with diets based on extruded whole grain red (RSD) or white sorghum (WSD), and control diet (CD) up to 60 days. The animals fed with sorghum diets consumed less and gained less weight compared to those fed with CD, but the efficiency of all diets was similar. Calcium intake was lower in animals fed with sorghum diets, related to the lower total intake of these animals. Apparent calcium absorption in animals fed with RSD was lower than in those fed with CD (CD: 72.7%, RSD: 51.0%, WSD: 64.8%). No significant differences in bone mineral density of total body, spin, femur, distal femur, tibia and proximal tibia were observed among the groups. However, Ca and P contents in the right femur of the rats consuming RSD were lower, indicating a certain imbalance in the metabolism of these minerals.

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翻译标题与摘要 下载文献
来源期刊:Skeletal radiology
作者列表:["Schaffler-Schaden D","Kneidinger C","Schweighofer-Zwink G","Flamm M","Iglseder B","Pirich C"]

METHODS:OBJECTIVE:Controversy exists about the impact of bone mineral density (BMD) and fracture risk in newly diagnosed patients with breast cancer (BC). It is presumed that there are differences in BMD between women with BC and healthy controls. BMD is therefore considered as a potential marker to predict BC risk. This study was conducted to investigate the association of BMD, trabecular bone score (TBS) and fracture risk in younger postmenopausal women with hormone responsive BC. METHODS:Overall, 343 women were examined. Women with BC were matched to a control group of the general population. Forty-nine women and fifty-nine controls were included in the final analysis. All subjects underwent dual energy x-ray absorptiometry (DXA) of the lumbar spine, femoral neck, and the total hip to evaluate bone mineral density. The 10-year fracture risk for a major osteoporotic fracture was assessed using the FRAX-score and the TBS-adjusted FRAX-Score, respectively. RESULTS:Lumbar and femoral neck BMD were similar in BC patients and controls. No difference was found for TBS of the spine (1.38 ± 0.1 vs.1.36 ± 0.09) in the BC and the control group, respectively (p = 0.19). The 10- year probability for a major osteoporotic fracture (MoF) or femoral neck (FN) fracture was 6.1 (± 2.6%) and 0.9 (± 1.2%) in the BC group vs. 6.7 (± 3.5%) (p = 0.33) and 0.9 (± 1.1%) (p = 0.73) in the control group. CONCLUSION:Postmenopausal women younger than 60 years with breast cancer do not show any differences in baseline BMD, TBS, or TBS adjusted FRAX in comparison to controls.

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作者列表:["Gurumurthy B","Tucci MA","Fan LW","Benghuzzi HA","Pal P","Bidwell GL","Salazar Marocho SM","Cason Z","Gordy D","Janorkar AV"]

METHODS::The goals of this study are to evaluate the ability of the multicomponent collagen-elastin-like polypeptide (ELP)-Bioglass scaffolds to support osteogenesis of rat mesenchymal stem cells (rMSCs), demonstrate in vivo biocompatibility by subcutaneous implantation in Sprague-Dawley rats, monitor degradation noninvasively, and finally assess the scaffold's ability in healing critical-sized cranial bone defects. The collagen-ELP-Bioglass scaffold supports the in vitro osteogenic differentiation of rMSCs over a 3 week culture period. The cellular (rMSC-containing) or acellular scaffolds implanted in the subcutaneous pockets of rats do not cause any local or systemic toxic effects or tumors. The real-time monitoring of the fluorescently labeled scaffolds by IVIS reveals that the scaffolds remain at the site of implantation for up to three weeks, during which they degrade gradually. Micro-CT analysis shows that the bilateral cranial critical-sized defects created in rats lead to greater bone regeneration when filled with cellular scaffolds. Bone mineral density and bone microarchitectural parameters are comparable among different scaffold groups, but the histological analysis reveals increased formation of high-quality mature bone in the cellular group, while the acellular group has immature bone and organized connective tissue. These results suggest that the rMSC-seeded collagen-ELP-Bioglass composite scaffolds can aid in better bone healing process.

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