title: Pomegranate Peel Extract Prevents Bone Loss in a Preclinical Model of Osteoporosis and Stimulates Osteoblastic Differentiation in Vitro.
abstract: 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.
authors.affiliation: Unité de Nutrition Humaine, CRNH Auvergne, UMR 1019, INRA, F-63000 Clermont-Ferrand, France. mel.spilmont@gmail.com.|Unité de Nutrition Humaine, Université d'Auvergne, Clermont Université, BP 10448, F-63000 Clermont-Ferrand, France. mel.spilmont@gmail.com.|GREENTECH SA Biopôle Clermont-Limagne, F-63360 Saint-Beauzire, France. mel.spilmont@gmail.com.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Spilmont
authors.affiliation: Unité de Nutrition Humaine, CRNH Auvergne, UMR 1019, INRA, F-63000 Clermont-Ferrand, France. laurent.leotoing@clermont.inra.fr.|Unité de Nutrition Humaine, Université d'Auvergne, Clermont Université, BP 10448, F-63000 Clermont-Ferrand, France. laurent.leotoing@clermont.inra.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Léotoing
authors.affiliation: Unité de Nutrition Humaine, CRNH Auvergne, UMR 1019, INRA, F-63000 Clermont-Ferrand, France. marie-jeanne.davicco@clermont.inra.fr.|Unité de Nutrition Humaine, Université d'Auvergne, Clermont Université, BP 10448, F-63000 Clermont-Ferrand, France. marie-jeanne.davicco@clermont.inra.fr.
authors.forename: Marie-Jeanne
authors.initials: MJ
authors.lastname: Davicco
authors.affiliation: Unité de Nutrition Humaine, CRNH Auvergne, UMR 1019, INRA, F-63000 Clermont-Ferrand, France. Patrice.Lebecque@clermont.inra.fr.|Unité de Nutrition Humaine, Université d'Auvergne, Clermont Université, BP 10448, F-63000 Clermont-Ferrand, France. Patrice.Lebecque@clermont.inra.fr.
authors.forename: Patrice
authors.initials: P
authors.lastname: Lebecque
authors.affiliation: Imagerie Moléculaire et Thérapie Vectorisée, Université d'Auvergne, Clermont Université, UMR 990, INSERM, BP 10448, F-63000 Clermont-Ferrand, France. elisabeth.noirault@inserm.fr.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Miot-Noirault
authors.affiliation: Laboratoire d'Ingénierie Ostéo-Articulaire et Dentaire-LIOAD, Université de Nantes, UMR 791, INSERM, F-44042 Nantes, France. paul.pilet@univ-nantes.fr.
authors.forename: Paul
authors.initials: P
authors.lastname: Pilet
authors.affiliation: GREENTECH SA Biopôle Clermont-Limagne, F-63360 Saint-Beauzire, France. laurent.rios@vetagro-sup.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Rios
authors.affiliation: Unité de Nutrition Humaine, CRNH Auvergne, UMR 1019, INRA, F-63000 Clermont-Ferrand, France. yohann.wittrant@clermont.inra.fr.|Unité de Nutrition Humaine, Université d'Auvergne, Clermont Université, BP 10448, F-63000 Clermont-Ferrand, France. yohann.wittrant@clermont.inra.fr.
authors.forename: Yohann
authors.initials: Y
authors.lastname: Wittrant
authors.affiliation: Unité de Nutrition Humaine, CRNH Auvergne, UMR 1019, INRA, F-63000 Clermont-Ferrand, France. veronique.coxam@clermont.inra.fr.|Unité de Nutrition Humaine, Université d'Auvergne, Clermont Université, BP 10448, F-63000 Clermont-Ferrand, France. veronique.coxam@clermont.inra.fr.
authors.forename: Véronique
authors.initials: V
authors.lastname: Coxam
mesh_terms: D016475:3T3 Cells; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D005638:Fruit / Q000737:chemistry; D029561:Lythraceae / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D010024:Osteoporosis / Q000517:prevention & control*; D010052:Ovariectomy; D010936:Plant Extracts / Q000494:pharmacology*; D000067996:RAW 264.7 Cells
chemical_list: D000975:Antioxidants; D010936:Plant Extracts; D000469:Alkaline Phosphatase
keywords: animal model; bone health; cell lines; nutritional prevention; pomegranate peel extract