Pomegranate Peel Extract Prevents Bone Loss in a Preclinical Model of Osteoporosis and Stimulates Osteoblastic Differentiation in Vitro

The nutritional benefits of pomegranate have attracted great scientific interest. The pomegranate, including the pomegranate peel, has been used worldwide for many years as a fruit with medicinal activity, mostly antioxidant properties. Among chronic diseases, osteoporosis, which is associated with bone remodelling impairment leading to progressive bone loss, could eventually benefit from antioxidant compounds because of the involvement of oxidative stress in the pathogenesis of osteopenia. In this study, with in vivo and ex vivo experiments, we investigated whether the consumption of pomegranate peel extract (PGPE) could limit the process of osteopenia. We demonstrated that in ovariectomized (OVX) C57BL/6J mice, PGPE consumption was able to significantly prevent the decrease in bone mineral density (-31.9%; p < 0.001 vs. OVX mice) and bone microarchitecture impairment. Moreover, the exposure of RAW264.7 cells to serum harvested from mice that had been given a PGPE-enriched diet elicited reduced osteoclast differentiation and bone resorption, as shown by the inhibition of the major osteoclast markers. In addition, PGPE appeared to substantially stimulate osteoblastic MC3T3-E1 alkaline phosphatase (ALP) activity at day 7, mineralization at day 21 and the transcription level of osteogenic markers. PGPE may be effective in preventing the bone loss associated with ovariectomy in mice, and offers a promising alternative for the nutritional management of this disease

Increased bioavailability of hesperetin-7-glucoside compared with hesperidin results in more efficient prevention of bone loss in adult ovariectomised rats

Hesperidin (Hp), a citrus flavonoid predominantly found in oranges, shows bone-sparing effects in ovariectomised (OVX) animals. In human subjects, the bioavailability of Hp can be improved by the removal of the rhamnose group to yield hesperetin-7-glucoside (H-7-glc). The aim of the present work was to test whether H-7-glc was more bioavailable and therefore more effective than Hp in the prevention of bone loss in the OVX rat. Adult 6-month-old female Wistar rats were sham operated or OVX, then pair fed for 90d a casein-based diet supplemented or not with freeze-dried orange juice enriched with Hp or H-7-glc at two dose equivalents of the hesperetin aglycone (0·25 and 0·5%). In the rats fed 0·5%, a reduction in OVX-induced bone loss was observed regarding total bone mineral density (BMD):+7·0% in OVX rats treated with Hp (HpOVX) and +6·6% in OVX rats treated with H-7-glc (H-7-glcOVX) v. OVX controls (P<0·05). In the rats fed 0·25% hesperetin equivalents, the H-7-glcOVX group showed a 6·6% improvement in total femoral BMD v. the OVX controls (P<0·05), whereas the Hp diet had no effect at this dose. The BMD of rats fed 0·25% H-7-glc was equal to that of those given 0·5% Hp, but was not further increased at 0·5% H-7-glc. Plasma hesperetin levels and relative urinary excretion were significantly enhanced in the H-7-glc v. Hp groups, and the metabolite profile showed the absence of eriodictyol metabolites and increased levels of hesperetin sulphates. Taken together, improved bioavailability of H-7-glc may explain the more efficient bone protection of this compoun

EB 1089, a vitamin D analog, decreases rat fetal calcium content

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Consumption of fermented milk containing blueberry, enriched with calcium and vitamin D positively modulates bone metabolism in postmenopausal women

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EB 1089, a vitamin D analog, decreases rat fetal calcium content

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The flavonoid fisetin promotes osteoblasts differentiation through Runx2 transcriptional activity

Scope: Flavonoids represent a group of polyphenolic compounds commonly found in daily nutrition with proven health benefits. Among this group, the flavonol fisetin has been previously shown to protect bone by repressing osteoclast differentiation. In the present study, we investigated the role of fisetin in regulating osteoblasts physiology. Methods and results: In vivo mice treated with LPSs exhibited osteoporosis features associated with a dramatic repression of osteoblast marker expression. In this model, inhibition of osteocalcin and type I collagen alpha 1 transcription was partially countered by a daily consumption of fisetin. Interestingly, in vitro, fisetin promoted both osteoblast alkaline phosphatase activity and mineralization process. To decipher how fisetin may exert its positive effect on osteoblastogenesis, we analyzed its ability to control the runt-related transcription factor 2 (Runx2), a key organizer in developing and maturing osteoblasts. While fisetin did not impact Runx2 mRNA and protein levels, it upregulated its transcriptional activity. Actually, fisetin stimulated the luciferase activity of a reporter plasmid driven by the osteocalcin gene promoter that contains Runx2 binding sites and promoted the mRNA expression of osteocalcin and type I collagen alpha 1 targets. Conclusion: Bone sparing properties of fisetin also rely on its positive influence on osteoblast differentiation and activity

GPR40 activation by high fat diet decreased bone loss in ovariectomized mouse model

National audiencePurpose: GPR40, a free fatty acid receptor, has been shown both in vivo and in vitro to prevent from bone loss by mainly targeting osteoclast resorption activity with a synthetic agonist GW9508. Here, we questioned whether stimulation of the GPR40 receptor by high-fat diet enriched with long chain fatty acids, natural ligands of GPR40, may parallel with its described beneficial effects on bone. Methods: In this study, 9 week-old sham-operated and ovariectomized C57/BL6 wild-type and GPR40-/- mice were fed with control or ANC high-fat diets for 5 weeks. Bone mineral density, body composition, weigh, inflammation and serum circulating bone remodeling parameters were monitored. Results: Although ANC high-fat diet induced a decrease of BMD in sham-operated wild-type, under ovariectomy conditions, mice fed with ANC high-fat diet have a significant higher BMD than GPR40-/- mice. This effect seems to be due to a modulation of the osteoblast/osteoclast coupling by stimulation of GPR40 by fatty acids. Conclusions: In this study, wedemonstrated for the first time that GPR40 limits bone loss induced by ovariectomy upon high fat diet. Taken together; our results demonstrate that GPR40 could mediate beneficial effects of fatty acids mainly by targeting the bone cell coupling and subsequent osteoclastic bone resorptio

GPR40 limits bone loss induced by ovariectomy upon high fat diet

National audienceWe formerly demonstrated that GPR40 prevents from osteoporosis establishment using synthetic agonist. Here, we questioned whether stimulation of GPR40 by fatty acids, the natural ligands for GPR40, may parallel with its described beneficial effects on bone. In this study we demonstrated for the first time that GPR40 limits bone loss induced by ovariectomy upon high fat diet. Taken together, our results demonstrate that GPR40 mediates beneficial effects of high fat diets mainly by targeting the bone cell coupling and subsequent osteoclastic bone resorption

GPR40 reveals the good side of deleterious diets

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Third metacarpal bone mineral density assessment in the standing horse by dual X-day absorptiometry suitability, precision and accuracy

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