title: Vanillic acid exerts oestrogen-like activities in osteoblast-like UMR 106 cells through MAP kinase (MEK/ERK)-mediated ER signaling pathway.
abstract: Sambucus williamsii Hance (SWH) has been used for treatment of bone and joint disease in China for thousands of years. Our previous study showed that SWH extract and its bioactive fraction could effectively prevent oestrogen-deficiency induced bone loss in ovariectomized mice. The present study aimed to study the bone protective effects of vanillic acid (VA), a phenolic acid isolated from the bioactive fraction of SWH, and to characterize the signaling pathways that mediated its actions in rat osteoblast-like UMR 106 cells. VA significantly stimulated proliferation, alkaline phosphatase (ALP) activities as well as significantly altered the mRNA expression of genes involved in osteoblast functions and osteoclastogenesis in UMR 106 cells. Co-treatment of UMR 106 cells with 10(-6)M ICI182,780 (a specific oestrogen receptor (ER) antagonist) abolished the stimulatory effects of VA on osteoblast proliferation and ALP activities, suggesting the role of ER in mediating its actions. However, VA (10(-12) to 10(-6)M) failed to bind to ERα or ERβ and did not activate oestrogen response element (ERE)-luciferase activities via ERα or ERβ in UMR 106 cells. In contrast, 10(-10) and 10(-8)M of VA induced the phosphorylation of MEK 1/2, ERK1/2 and ERα at Ser118 residue in UMR 106 cells, suggesting that MAP kinase-mediated pathway is involved in mediating its actions. Taken together, our results indicated that VA is a bioactive compound in SWH that exerts stimulatory effects in osteoblast-like cells via non-genomic, but not classical, ER signaling pathway.
authors.affiliation: State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen Research Institute of The Hong Kong Polytechnic University, Shenzhen 518057, PR China; Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, PR China.
authors.forename: Hui-Hui
authors.initials: HH
authors.lastname: Xiao
authors.affiliation: Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, PR China.
authors.forename: Quan-Gui
authors.initials: QG
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen Research Institute of The Hong Kong Polytechnic University, Shenzhen 518057, PR China; Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, PR China.
authors.forename: Ka-Chung
authors.initials: KC
authors.lastname: Wong
authors.affiliation: Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Institute of Traditional Chinese Medicine & Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, PR China.
authors.forename: Xin-Sheng
authors.initials: XS
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Chinese Medicine and Molecular Pharmacology (Incubation), Shenzhen Research Institute of The Hong Kong Polytechnic University, Shenzhen 518057, PR China; Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, PR China. Electronic address: bcmswong@polyu.edu.hk.
authors.forename: Man-Sau
authors.initials: MS
authors.lastname: Wong
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics; D053244:Osteoprotegerin / Q000235:genetics; D053245:RANK Ligand / Q000235:genetics; D051381:Rats; D014641:Vanillic Acid / Q000494:pharmacology*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D053244:Osteoprotegerin; D053245:RANK Ligand; C493717:Runx2 protein, rat; C506032:Tnfrsf11b protein, rat; D015675:Osteocalcin; D000469:Alkaline Phosphatase; D014641:Vanillic Acid; D002118:Calcium
keywords: MAP kinase mediated pathway; Osteoblast; Phenolic acid; Sambucus williamsii Hance; Vanillic acid