title: Molecular mechanism of hesperetin-7-O-glucuronide, the main circulating metabolite of hesperidin, involved in osteoblast differentiation.
abstract: Citrus fruit hesperidin is hydrolyzed by gut microflora into aglycone form (hesperetin) and then conjugated mainly into glucuronides. We previously demonstrated that hesperetin enhanced osteoblast differentiation. In this study, we examined the effect of hesperetin-7-O-glucuronide (Hp7G) on primary rat osteoblast proliferation and differentiation. The impact of Hp7G on specific bone signaling pathways was explored. Osteoblasts were exposed to physiological concentrations of 1 (Hp7G1) and 10 (Hp7G10) microM of conjugate. The glucuronide did not affect proliferation but enhanced differentiation by significantly increasing alkaline phosphatase (ALP) activity from day 14 of exposure. Hp7G significantly induced mRNA expression of ALP, Runx2, and Osterix after 48 h of exposure. Moreover, phosphorylation of Smad1/5/8 was enhanced by Hp7G, while ERK1/2 remained unchanged after 48 h. Hp7G decreased RANKL gene expression. These results suggest that Hp7G may regulate osteoblast differentiation through Runx2 and Osterix stimulation, and might be implicated in the regulation of osteoblast/osteoclast communication.
authors.affiliation: INRA Clermont-Ferrand/Theix, Human Nutrition Unit UMR1019, F-63122 St. Genes Champanelle, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Trzeciakiewicz
authors.forename: Veronique
authors.initials: V
authors.lastname: Habauzit
authors.forename: Sylvie
authors.initials: S
authors.lastname: Mercier
authors.forename: Denis
authors.initials: D
authors.lastname: Barron
authors.forename: Mireia
authors.initials: M
authors.lastname: Urpi-Sarda
authors.forename: Claudine
authors.initials: C
authors.lastname: Manach
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Offord
authors.forename: Marie-Noelle
authors.initials: MN
authors.lastname: Horcajada
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D020719:Glucuronides / Q000378:metabolism / Q000494:pharmacology*; D006569:Hesperidin / Q000378:metabolism* / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020719:Glucuronides; D006569:Hesperidin; C013015:hesperetin