title: Costunolide stimulates the function of osteoblastic MC3T3-E1 cells.
abstract: The effect of costunolide on the function of osteoblastic MC3T3-E1 cells was studied. Costunolide significantly increased the growth of MC3T3-E1 cells and caused a significant elevation of alkaline phosphatase (ALP) activity, collagen content, and mineralization in the cells (P<0.05). The effect of costunolide in increasing cell growth was completely prevented by the presence of ICI182780, LY294002, PD98059, rotlerin, or glibenclamide, suggesting that the effect of costunolide might be partly mediated from estrogen receptor (ER), PI3K, ERK, protein kinase C (PKC) and mitochondrial ATP-sensitive K(+) channel. The effect of costunolide in increasing ALP activity was prevented by the presence of ICI182780, PD98059, SB203580, or rotrelin, suggesting that the effect of costunolide on ALP activity might be mediated from ER, ERK, p38, and PKC. The effect of costunolide in increasing collagen content was prevented by the presence of LY294002, PD98059, SB203580, SP600125, or rotrelin, suggesting that the effect of costunolide on collagen synthesis might be mediated from PI3K, ERK, p38, JNK, and PKC. Moreover, cotreatment of ICI182780 or LY294002 inhibited costunolide-mediated upregulation of mineralization, suggesting that the induction of mineralization by costunolide is associated with increased activation of ER and PI3K. Our data indicate that the enhancement of osteoblast function by costunolide may result in the prevention for osteoporosis.
authors.affiliation: Department of Food & Nutrition, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul, Republic of Korea.
authors.forename: Young Soon
authors.initials: YS
authors.lastname: Lee
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Choi
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism*; D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects; D002460:Cell Line; D003094:Collagen / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000077267:Fulvestrant; D054086:KATP Channels / Q000378:metabolism; D051379:Mice; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010024:Osteoporosis / Q000378:metabolism / Q000517:prevention & control*; D011494:Protein Kinases / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D007783:Lactones
chemical_list: D000469:Alkaline Phosphatase; D003094:Collagen; D004791:Enzyme Inhibitors; D004958:Estradiol; D000077267:Fulvestrant; D054086:KATP Channels; D019001:Nitric Oxide Synthase; D011494:Protein Kinases; D012717:Sesquiterpenes; C002602:costunolide; D007783:Lactones