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Icariin (ICA) is the main active flavonoid glucoside from herbs of the genus Epimedium ; in traditional Chinese medicine, these herbs have long been prescribed for the treatment of bone fractures and osteoporosis. Several studies have shown that treatment with ICA can increase osteogenic differentiation and reduce bone loss in vivo and in vitro. However, the definite signaling pathway of this osteogenic effect remains unclear. In this study, we selected bone morphogenetic protein 2 (BMP2)-induced osteoblastic differentiation of multipotent mesenchymal progenitor C2C12 cells as a model of osteoblast differentiation. We investigated the effects of ICA on C2C12 cells osteogenic differentiation and the underlying molecular mechanisms. We found that ICA could enhance BMP2-mediated osteoblastic differentiation of C2C12 cells in a dose-dependent manner. Treatment with ICA activated the cAMP/PKA/CREB signaling axis in a time-dependent manner. Blocking cAMP signaling using the PKA selective inhibitor H89 significantly inhibited the stimulatory effect of ICA on osteogenesis. Therefore, the osteoinductive potential and the low cost of ICA indicate that it is a promising alternative treatment or promoter for enhancing the therapeutic effects of BMP2.

Titel:	Icariin Promotes the Osteogenic Action of BMP2 by Activating the cAMP Signaling Pathway.
Autor/in / Beteiligte Person:	Chen, M ; Cui, Y ; Li, H ; Luan, J ; Zhou, X ; Han, J
Link:	Zum Volltext
Zeitschrift:	Molecules (Basel, Switzerland), Jg. 24 (2019-10-28), Heft 21
Veröffentlichung:	Basel, Switzerland : MDPI, c1995-, 2019
Medientyp:	academicJournal
ISSN:	1420-3049 (electronic)
DOI:	10.3390/molecules24213875
Schlagwort:	Animals Bone Resorption genetics Bone Resorption pathology Cyclic AMP genetics Epimedium chemistry Fractures, Bone drug therapy Humans Intracellular Signaling Peptides and Proteins pharmacology Medicine, Chinese Traditional Mesenchymal Stem Cells drug effects Mice Osteoblasts drug effects Osteogenesis genetics Osteoporosis drug therapy Signal Transduction drug effects Bone Morphogenetic Protein 2 pharmacology Bone Resorption drug therapy Cell Differentiation drug effects Flavonoids pharmacology Osteogenesis drug effects
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Molecules] 2019 Oct 28; Vol. 24 (21). <i>Date of Electronic Publication: </i>2019 Oct 28. MeSH Terms: Bone Morphogenetic Protein 2 / pharmacology ; Bone Resorption / drug therapy ; Cell Differentiation / drug effects ; Flavonoids / pharmacology ; Osteogenesis / *drug effects ; Animals ; Bone Resorption / genetics ; Bone Resorption / pathology ; Cyclic AMP / genetics ; Epimedium / chemistry ; Fractures, Bone / drug therapy ; Humans ; Intracellular Signaling Peptides and Proteins / pharmacology ; Medicine, Chinese Traditional ; Mesenchymal Stem Cells / drug effects ; Mice ; Osteoblasts / drug effects ; Osteogenesis / genetics ; Osteoporosis / drug therapy ; Signal Transduction / drug effects References: Spine (Phila Pa 1976). 2008 Dec 15;33(26):2843-9. (PMID: 19092613) ; Proc Natl Acad Sci U S A. 2008 May 20;105(20):7281-6. (PMID: 18490653) ; J Cell Biol. 1994 Dec;127(6 Pt 1):1755-66. (PMID: 7798324) ; Bone. 2006 Feb;38(2):206-14. (PMID: 16203197) ; Evid Based Complement Alternat Med. 2013;2013:652317. (PMID: 24348713) ; Eur J Clin Invest. 2012 Dec;42(12):1332-41. (PMID: 22998735) ; J Bone Miner Metab. 2008;26(5):478-84. (PMID: 18758906) ; Pharmazie. 2007 May;62(5):388-91. (PMID: 17557750) ; Life Sci. 2007 Aug 16;81(10):832-40. (PMID: 17764702) ; Bone. 2008 Apr;42(4):806-18. (PMID: 18234576) ; Planta Med. 2013 Nov;79(16):1501-8. (PMID: 24072503) ; Bone. 2002 Sep;31(3):396-401. (PMID: 12231412) ; J Neurosurg Spine. 2010 Jan;12(1):40-6. (PMID: 20043763) ; Bone. 2014 Sep;66:189-98. (PMID: 24956021) ; Tissue Eng Part A. 2012 Mar;18(5-6):558-67. (PMID: 21942968) ; Menopause. 2014 Sep;21(9):1007-16. (PMID: 24552978) ; Phytomedicine. 2012 Aug 15;19(11):1035-41. (PMID: 22818561) ; Planta Med. 2019 Apr;85(6):473-482. (PMID: 30703815) ; J Cell Biochem. 2019 Aug;120(8):13121-13132. (PMID: 30887562) ; Phytochemistry. 2007 May;68(10):1448-58. (PMID: 17434191) ; J Biol Chem. 1998 Mar 27;273(13):7547-53. (PMID: 9516456) ; Sci Rep. 2019 Mar 27;9(1):5249. (PMID: 30918282) ; Molecules. 2019 May 15;24(10):null. (PMID: 31096652) ; Biochimie. 2012 Dec;94(12):2514-22. (PMID: 22796380) ; Gene. 2005 Aug 29;357(1):1-8. (PMID: 16125875) ; Phytomedicine. 2011 Jan 15;18(2-3):176-85. (PMID: 20554188) ; J Endocrinol Invest. 2006 Feb;29(2):101-8. (PMID: 16610234) ; Endocr Rev. 2017 Jun 1;38(3):255-266. (PMID: 28472361) ; Oral Dis. 2017 Nov;23(8):1021-1028. (PMID: 27976475) ; Cell Biochem Biophys. 2013 Sep;67(1):189-97. (PMID: 23417569) ; Int J Mol Med. 2012 Oct;30(4):889-95. (PMID: 22842877) ; Bone. 2009 May;44(5):872-7. (PMID: 19442611) ; J Biol Chem. 2017 Dec 22;292(51):20883-20896. (PMID: 29089388) ; Toxicol Appl Pharmacol. 2019 Sep 15;379:114639. (PMID: 31251943) ; Endocr Rev. 2003 Apr;24(2):218-35. (PMID: 12700180) ; Nutrients. 2019 May 18;11(5):null. (PMID: 31109081) ; Molecules. 2011 Dec 06;16(12):10123-33. (PMID: 22146373) ; J Exp Clin Cancer Res. 2015 Feb 15;34:17. (PMID: 25887673) ; Eur J Pharmacol. 2013 Aug 15;714(1-3):15-22. (PMID: 23764463) ; Evid Based Complement Alternat Med. 2005 Sep;2(3):353-61. (PMID: 16136213) ; JAMA. 2009 Jul 1;302(1):58-66. (PMID: 19567440) ; Biomed Pharmacother. 2016 Dec;84:931-939. (PMID: 27764755) ; Biotechnol Lett. 2009 Dec;31(12):1825-35. (PMID: 19690811) ; Int Immunopharmacol. 2012 Jan;12(1):74-9. (PMID: 22056950) ; Biochem Biophys Res Commun. 2008 May 2;369(2):444-8. (PMID: 18295595) ; Oxid Med Cell Longev. 2019 Apr 22;2019:7940808. (PMID: 31178973) ; Exp Ther Med. 2016 Jun;11(6):2399-2406. (PMID: 27284327) ; Phytother Res. 2009 Jan;23(1):116-22. (PMID: 18803231) ; Clin Cases Miner Bone Metab. 2011 Sep;8(3):37-43. (PMID: 22461828) ; Planta Med. 2000 Mar;66(2):119-23. (PMID: 10763583) Contributed Indexing: Keywords: BMP2; Icariin (ICA); Osteoblast differentiation; cAMP/PKA/CREB Substance Nomenclature: 0 (Bmp2 protein, mouse) ; 0 (Bone Morphogenetic Protein 2) ; 0 (Flavonoids) ; 0 (Intracellular Signaling Peptides and Proteins) ; 0 (protein kinase modulator) ; E0399OZS9N (Cyclic AMP) ; VNM47R2QSQ (icariin) Entry Date(s): Date Created: 20191031 Date Completed: 20200313 Latest Revision: 20200313 Update Code: 20240513 PubMed Central ID: PMC6864436

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Icariin Promotes the Osteogenic Action of BMP2 by Activating the cAMP Signaling Pathway.