Icariin protects against bone loss induced by oestrogen deficiency and activates oestrogen receptor-dependent osteoblastic functions in UMR 106 cells.
OBJECTIVE
Icariin may be the active ingredient in Herba Epimedii, a Chinese herb commonly used for treatment of osteoporosis. The present study aims to delineate the mechanism(s) by which icariin prevents bone loss after ovariectomy (OVX) in vivo and stimulates osteoblastic functions in vitro.


METHODS
Ovariectomized or sham-operated C57BL/6 mice were treated with vehicle, 17beta-oestradiol or icariin for 6 weeks. Total and trabecular bome mineral density (BMD) as well as polar stress-strain index of distal femur were measured by peripheral computed tomography. The mRNA expressions of OPG and RANKL in tibia were studied by RT-PCR. Interactions between the oestrogen receptor (ER) antagonist ICI182,780 and icariin were studied in UMR 106 cells. The functional transactivation of ERalpha and ERbeta as well as ERalpha phosphorylation by icariin were also assessed.


RESULTS
Icariin suppressed the loss of bone mass and strength in distal femur and increased the mRNA expression ratio of OPG/RANKL in tibia, following OVX. Icariin increased ER-dependent cell proliferation, alkaline phosphatase (ALP) activity, gene expression of OPG and the OPG/RANKL ratio in UMR 106 cells. Icariin did not activate ERE-luciferase activity in UMR 106 cells, via the ERalpha or the ERbeta-mediated pathway, but it did increase ERalpha phosphorylation at Ser118.


CONCLUSIONS
Our results indicate that icariin exerts anabolic effects in bone possibly by activating ER in a ligand-independent manner. Its ability to prevent OVX-induced bone loss without inducing uterotrophic effects supports its use as an alternative regimen for management of postmenopausal osteoporosis.
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong.
Sao-Keng
SK
Mok
Wen-Fang
WF
Chen
Wan-Ping
WP
Lai
Ping-Chung
PC
Leung
Xin-Luan
XL
Wang
Xin-Sheng
XS
Yao
Man-Sau
MS
Wong
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D005269:Femur / Q000187:drug effects / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D000077267:Fulvestrant; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D053244:Osteoprotegerin / Q000235:genetics; D010052:Ovariectomy; D010766:Phosphorylation; D053245:RANK Ligand / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013977:Tibia / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D014162:Transfection
D050071:Bone Density Conservation Agents; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D005419:Flavonoids; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; C506031:Tnfrsf11b protein, mouse; C506032:Tnfrsf11b protein, rat; C505689:Tnfsf11 protein, mouse; D000077267:Fulvestrant; D004958:Estradiol; D000469:Alkaline Phosphatase; C056599:icariin