title: Icariin is more potent than genistein in promoting osteoblast differentiation and mineralization in vitro.
abstract: There has been a strong interest in searching for natural therapies for osteoporosis. Genistein, an isoflavone abundant in soy, and icariin, a prenylated flavonol glycoside isolated from Epimedium Herb, have both been identified to exert beneficial effects in preventing postmenopausal bone loss. However, the relative potency in osteogenesis between the individual phytoestrogen flavonoids remains unknown. The present study compared ability of genistein and icariin in enhancing differentiation and mineralization of cultured rat calvarial osteoblasts in vitro. Dose-dependent studies in osteoblast differentiation measuring alkaline phosphatase (ALP) activity revealed optimal concentrations of genistein and icarrin for stimulating osteogenesis to be both at 10(-5) M. Time course studies comparing the two compounds both at 10(-5) M demonstrated that icariin treatment always produced higher ALP activity, more and larger areas of CFU-F(ALP) colonies and mineralized nodules, more osteocalcin secretion, and calcium deposition, and a higher level of mRNA expression of osteogenesis-related genes COL1α2, BMP-2, OSX, and RUNX-2. However, they inhibited the proliferation of osteoblasts to a similar degree. In conclusion, although future in vivo studies are required to investigate whether icariin is more efficient in improving bone mass and/or preventing bone loss, our in vitro studies have demonstrated that icariin has a stronger osteogenic activity than genistein. In addition, while the prenyl group on C-8 of icariin could be the active group that takes part in osteoblastic differentiation and explains its greater potency in osteogenesis, mechanisms of action, and reasons for the relative potency of icariin versus genistein need to be further studied.
authors.affiliation: Department of Pharmacy, Lanzhou General Hospital, Lanzhou Command of CPLA, Lanzhou 730050, People's Republic of China.
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Ma
authors.forename: Lei-Guo
authors.initials: LG
authors.lastname: Ming
authors.forename: Bao-Feng
authors.initials: BF
authors.lastname: Ge
authors.forename: Yuan-Kun
authors.initials: YK
authors.lastname: Zhai
authors.forename: Peng
authors.initials: P
authors.lastname: Song
authors.forename: Cory J
authors.initials: CJ
authors.lastname: Xian
authors.forename: Ke-Ming
authors.initials: KM
authors.lastname: Chen
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000096:biosynthesis / Q000235:genetics; D002113:Calcification, Physiologic / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis / Q000235:genetics; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D057075:Enzyme Assays; D005419:Flavonoids / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012886:Skull / Q000166:cytology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
chemical_list: D055396:Bone Morphogenetic Protein 2; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D012333:RNA, Messenger; C493717:Runx2 protein, rat; C495181:Sp7 protein, rat; D014157:Transcription Factors; D015675:Osteocalcin; D003094:Collagen; D019833:Genistein; D000469:Alkaline Phosphatase; D002118:Calcium; C056599:icariin