Osteogenic activity of silymarin through enhancement of alkaline phosphatase and osteocalcin in osteoblasts and tibia-fractured mice

Title
Osteogenic activity of silymarin through enhancement of alkaline phosphatase and osteocalcin in osteoblasts and tibia-fractured mice
Author(s)
정대원강영희[강영희]김정례[김정례]박신혜[박신혜]남주석[남주석]
Keywords
IN-VITRO MINERALIZATION; TRANSCRIPTIONAL REGULATION; BONE-DEVELOPMENT; DIFFERENTIATION; PATHWAY; EXPRESSION; PROTEINS; THERAPY; REPAIR; CELLS
Issue Date
201204
Publisher
ROYAL SOC MEDICINE PRESS LTD
Citation
EXPERIMENTAL BIOLOGY AND MEDICINE, v.237, no.4, pp.417 - 428
Abstract
Bone-remodeling imbalance induced by increased bone resorption and osteoclast formation is known to cause skeletal diseases such as osteoporosis. There has been growing interest in the anabolic natural agents that enhance bone formation. Silymarin is flavonolignans extracted from blessed milk thistle. Several studies suggest that silymarin possesses antihepatotoxic properties and anticancer effects against carcinoma cells. This study investigated promoting effects of silymarin on differentiation and mineralization of osteoblastic MC3T3-E1 mouse cells and on bone mineral density (BMD) by in vivo fracture experiments. Osteoblasts were treated with 1-20 mu mol/L silymarin for 15 days in a differentiating medium. In addition, this study explored signaling pathways implicated in the osteoblastogenesis of silymarin. It was found that silymarin stimulated alkaline phosphatase (ALP) activity and calcium nodule formation in a dose-dependent manner with a substantial effect on osteoblast proliferation. Silymarin treatment enhanced collagen secretion, osteocalcin transcription and bone morphogenetic protein (BMP) expression. The BMP inhibitor noggin suppressed the silymarin-promoted ALP activity in differentiated osteoblasts, suggesting that its osteoblastogenic actions entail the BMP pathway. This was proved by increased SMAD1/5/8 phosphorylation and runt-related transcription factor 2 (Runx2) expression in the presence of silymarin. In 21-day fracture-healing experiments, fractured and silymarin (10 mg/kg)-treated C57BL/6 mice showed better bone healing than fractured mice. Silymarin supplementation improved tibial bone strength with elevated BMD and serum levels of osteogenic ALP and osteocalcin. Taken together, these results demonstrate, for the first time, that silymarin has a potential to enhance osteoblastogenesis through accelerating BMP/SMAD/Runx2 signal pathways and to improve fracture healing and bone strength in mouse tibiae.
URI
http://hdl.handle.net/YU.REPOSITORY/28661http://dx.doi.org/10.1258/ebm.2011.011376
ISSN
1535-3702
Appears in Collections:
의과대학 > 미생물학교실 > Articles
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