STAT-3 regulation of CXCR4 is necessary for the prenylflavonoid Icaritin to enhance mesenchymal stem cell proliferation, migration and osteogenic differentiation.
Mesenchymal stem cell (MSC) dysfunction has been implicated in the pathogenesis of osteoporosis. MSCs derived from osteoporotic subjects demonstrate significant impairment in proliferation, adhesion and chemotaxis, and osteogenic differentiation, leading to reduced functional bone-forming osteoblasts and ultimately nett bone loss and osteoporosis. Epimedium herbs and its active compound Icaritin (ICT) have been used in Chinese ethnopharmacology for the treatment of metabolic bone diseases. Using an in-vitro cell culture model, we investigated the benefits of ICT treatment in enhancing MSC proliferation, migration and osteogenic differentiation, and provide novel data to describe its mechanism of action. ICT enhances MSC proliferation, chemotaxis to stromal cell-derived factor-1 (SDF-1) and osteogenic differentiation through the activation of signal transduction activator transcription factor 3 (STAT-3), with a consequential up-regulation in the expression and activity of cysteine (C)-X-C motif chemokine receptor 4 (CXCR4). These findings provide a strong basis for future clinical studies to confirm the therapeutic potential of ICT for the prevention and treatment of osteoporosis and fragility fractures.
['Lim|R Z L|RZL|', 'Li|L|L|', 'Yong|E L|EL|', 'Chew|N|N|']
D002118:Calcium D002448:Cell Adhesion D002454:Cell Differentiation D002455:Cell Division D002465:Cell Movement D002478:Cells, Cultured D050659:Core Binding Factor Alpha 1 Subunit D004353:Drug Evaluation, Preclinical D005419:Flavonoids D006801:Humans D059630:Mesenchymal Stem Cells D010006:Osteoblasts D010024:Osteoporosis D010766:Phosphorylation D011401:Promoter Regions, Genetic D011499:Protein Processing, Post-Translational D034622:RNA Interference D034741:RNA, Small Interfering D019718:Receptors, CXCR4 D050796:STAT3 Transcription Factor D014158:Transcription, Genetic D015854:Up-Regulation
Icaritin Proliferation Migration Osteogenic differentiation MSC Anabolic therapeutics