Icariin induces osteogenic differentiation in vitro in a BMP- and Runx2-dependent manner.
To effectively treat bone diseases using bone regenerative medicine, there is an urgent need to develop safe cheap drugs that can potently induce bone formation. Here, we demonstrate the osteogenic effect of icariin, the main active compound of Epimedium pubescens. Icariin induced osteogenic differentiation in pre-osteoblastic MC3T3-E1 cells and mouse primary osteoblasts. Icariin upregulated the mRNA expression levels of the osteoblast marker genes runt-related transcription factor 2 (Runx2) and inhibitor of DNA-binding 1 (Id-1). The osteogenic effect was inhibited by the introduction of Smad6 or dominant-negative Runx2, as well as Noggin treatment. Furthermore, icariin induced the mRNA expression of bone morphogenetic protein (BMP)-4. These data suggest that icariin exerts its potent osteogenic effect through induction of Runx2 expression, production of BMP-4 and activation of BMP signaling. The extremely low cost of icariin and its high abundance make it appealing for bone regenerative medicine.
Zhao
Jiyuan
J
Department of Chemistry and Biotechnology, School of Engineering, University of Tokyo, Tokyo 113-8656, Japan.
Ohba
Shinsuke
S
Shinkai
Masashige
M
Chung
Ung-Il
UI
Nagamune
Teruyuki
T
D041721:3T3-L1 Cells; D000818:Animals; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage; D005419:Flavonoids / Q000008:administration & dosage*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*
C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; C493716:Runx2 protein, mouse; C056599:icariin