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Background and Purpose: 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.

Experimental Approach: 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.

Key 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 and Implications: 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.

Titel:	Icariin protects against bone loss induced by oestrogen deficiency and activates oestrogen receptor-dependent osteoblastic functions in UMR 106 cells.
Autor/in / Beteiligte Person:	Mok, SK ; Chen, WF ; Lai, WP ; Leung, PC ; Wang, XL ; Yao, XS ; Wong, MS
Link:	Zum Volltext
Zeitschrift:	British journal of pharmacology, Jg. 159 (2010-02-01), Heft 4, S. 939-49
Veröffentlichung:	London : Wiley ; <i>Original Publication</i>: London, Macmillian Journals Ltd., 2010
Medientyp:	academicJournal
ISSN:	1476-5381 (electronic)
DOI:	10.1111/j.1476-5381.2009.00593.x
Schlagwort:	Alkaline Phosphatase metabolism Animals Bone Density drug effects Cell Line Cell Proliferation drug effects Disease Models, Animal Dose-Response Relationship, Drug Estradiol administration & dosage Estradiol analogs & derivatives Estradiol pharmacology Estrogen Antagonists pharmacology Estrogen Receptor alpha antagonists & inhibitors Estrogen Receptor alpha genetics Estrogen Receptor alpha metabolism Estrogen Receptor beta antagonists & inhibitors Estrogen Receptor beta genetics Estrogen Receptor beta metabolism Female Femur drug effects Femur metabolism Fulvestrant Gene Expression Regulation drug effects Mice Mice, Inbred C57BL Osteoblasts metabolism Osteoporosis diagnostic imaging Osteoporosis etiology Osteoporosis metabolism Osteoprotegerin genetics Phosphorylation RANK Ligand genetics RNA, Messenger metabolism Rats Tibia drug effects Tibia metabolism Time Factors Tomography, X-Ray Computed Transfection Bone Density Conservation Agents pharmacology Estrogen Receptor alpha agonists Estrogen Receptor beta agonists Estrogens deficiency Flavonoids pharmacology Osteoblasts drug effects Osteoporosis prevention & control Ovariectomy
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Br J Pharmacol] 2010 Feb; Vol. 159 (4), pp. 939-49. <i>Date of Electronic Publication: </i>2010 Jan 27. MeSH Terms: Ovariectomy* ; Bone Density Conservation Agents / pharmacology ; Estrogen Receptor alpha / agonists ; Estrogen Receptor beta / agonists ; Estrogens / deficiency ; Flavonoids / pharmacology ; Osteoblasts / drug effects ; Osteoporosis / *prevention & control ; Alkaline Phosphatase / metabolism ; Animals ; Bone Density / drug effects ; Cell Line ; Cell Proliferation / drug effects ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Estradiol / administration & dosage ; Estradiol / analogs & derivatives ; Estradiol / pharmacology ; Estrogen Antagonists / pharmacology ; Estrogen Receptor alpha / antagonists & inhibitors ; Estrogen Receptor alpha / genetics ; Estrogen Receptor alpha / metabolism ; Estrogen Receptor beta / antagonists & inhibitors ; Estrogen Receptor beta / genetics ; Estrogen Receptor beta / metabolism ; Female ; Femur / drug effects ; Femur / metabolism ; Fulvestrant ; Gene Expression Regulation / drug effects ; Mice ; Mice, Inbred C57BL ; Osteoblasts / metabolism ; Osteoporosis / diagnostic imaging ; Osteoporosis / etiology ; Osteoporosis / metabolism ; Osteoprotegerin / genetics ; Phosphorylation ; RANK Ligand / genetics ; RNA, Messenger / metabolism ; Rats ; Tibia / drug effects ; Tibia / metabolism ; Time Factors ; Tomography, X-Ray Computed ; Transfection References: Life Sci. 2007 Aug 16;81(10):832-40. (PMID: 17764702) ; Cell. 1989 Nov 3;59(3):477-87. (PMID: 2805068) ; Mol Cell Biol. 2007 Feb;27(4):1516-30. (PMID: 17158928) ; Nucleic Acids Res. 1989 Jul 25;17(14):5477-88. (PMID: 2762146) ; Bone. 2001 Sep;29(3):265-70. (PMID: 11557371) ; J Bone Miner Res. 2007 Jul;22(7):1072-9. (PMID: 17419678) ; Biochem Biophys Res Commun. 2008 Nov 14;376(2):404-8. (PMID: 18789310) ; Toxicology. 2001 Sep 14;166(1-2):79-89. (PMID: 11518614) ; Science. 1995 Dec 1;270(5241):1491-4. (PMID: 7491495) ; Chin Med J (Engl). 2007 Feb 5;120(3):204-10. (PMID: 17355822) ; Clin Orthop Relat Res. 2006 Feb;443:48-54. (PMID: 16462425) ; Mol Endocrinol. 1994 Jan;8(1):21-30. (PMID: 8152428) ; Mol Endocrinol. 2008 Feb;22(2):287-303. (PMID: 17962382) ; Pharmazie. 2007 May;62(5):388-91. (PMID: 17557750) ; Vitam Horm. 2001;62:231-52. (PMID: 11345900) ; Lancet. 2003 Aug 9;362(9382):419-27. (PMID: 12927427) ; JAMA. 2002 Jul 17;288(3):321-33. (PMID: 12117397) ; J Steroid Biochem Mol Biol. 2008 Jan;108(1-2):64-71. (PMID: 17936617) ; EMBO J. 1996 May 1;15(9):2174-83. (PMID: 8641283) ; Cell. 1986 Sep 26;46(7):1053-61. (PMID: 3463433) ; Phytomedicine. 2009 Apr;16(4):320-6. (PMID: 19269147) ; Annu Rev Plant Biol. 2004;55:225-61. (PMID: 15377220) ; Evid Based Complement Alternat Med. 2005 Sep;2(3):353-61. (PMID: 16136213) ; Oncogene. 2002 Jul 25;21(32):4921-31. (PMID: 12118371) ; Science. 2002 Oct 25;298(5594):843-6. (PMID: 12399595) ; Climacteric. 2007 Aug;10(4):273-5. (PMID: 17653953) ; Bone. 2003 Feb;32(2):136-41. (PMID: 12633785) ; Biochem Biophys Res Commun. 2008 May 2;369(2):444-8. (PMID: 18295595) ; Wei Sheng Yan Jiu. 2005 Mar;34(2):191-3. (PMID: 15952661) ; Mol Endocrinol. 1995 Apr;9(4):443-56. (PMID: 7659088) ; Br J Nutr. 2006 Jun;95(6):1039-47. (PMID: 16768824) ; Br J Pharmacol. 2008 Mar;153 Suppl 2:S1-209. (PMID: 18347570) ; Br J Pharmacol. 2009 Apr;156(7):1136-46. (PMID: 19298253) ; Drugs Aging. 2007;24(1):37-55. (PMID: 17233546) Substance Nomenclature: 0 (Bone Density Conservation Agents) ; 0 (Estrogen Antagonists) ; 0 (Estrogen Receptor alpha) ; 0 (Estrogen Receptor beta) ; 0 (Estrogens) ; 0 (Flavonoids) ; 0 (Osteoprotegerin) ; 0 (RANK Ligand) ; 0 (RNA, Messenger) ; 0 (Tnfrsf11b protein, mouse) ; 0 (Tnfrsf11b protein, rat) ; 0 (Tnfsf11 protein, mouse) ; 22X328QOC4 (Fulvestrant) ; 4TI98Z838E (Estradiol) ; EC 3.1.3.1 (Alkaline Phosphatase) ; VNM47R2QSQ (icariin) Entry Date(s): Date Created: 20100205 Date Completed: 20100709 Latest Revision: 20220408 Update Code: 20231215 PubMed Central ID: PMC2829219

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Icariin protects against bone loss induced by oestrogen deficiency and activates oestrogen receptor-dependent osteoblastic functions in UMR 106 cells.