Saponins from the roots of Platycodon grandiflorum stimulate osteoblast differentiation via p38 MAPK- and ERK-dependent RUNX2 activation.
Changkil (CK), the aqueous extract of the roots of Platycodon grandiflorum, has been used as a traditional oriental medicine for the treatment of chronic adult diseases. Although a saponin fraction derived from CK (CKS) has been suggested to have a variety of functional effects, its effect on bone is unknown. In the present study, the effects of CKS on osteoblast differentiation and function were determined by analyzing the activity of alkaline phosphatase (ALP), an osteoblast marker, and the regulation of RUNX2, a master gene of osteoblast differentiation, in a mesenchymal stem cell line. CKS upregulated ALP activity and the expression of osteogenic marker genes in C2C12 cells. In addition, CKS increased the expression and transcriptional activity of RUNX2. To determine which signaling pathways are involved in the osteogenic effects of CKS, we tested the effect of inhibitors of kinases known to regulate RUNX2. CKS-induced enhancement of RUNX2 and ALP was inhibited by treatment with a p38 inhibitor (SB203580) and an ERK inhibitor (U0126). These findings suggest that CKS stimulates osteoblast differentiation by activation of RUNX2 via mechanisms related to the p38 MAPK and ERK signaling pathways. The regulation of RUNX2 activation by CKS may be an important therapeutic target for osteoporosis.
Jeong
Hyung Min
HM
College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, South Korea.
Han
Eun Hee
EH
Jin
Yun Hey
YH
Hwang
Yong Pil
YP
Kim
Hyung Gyun
HG
Park
Bong Hwan
BH
Kim
Jin Young
JY
Chung
Young Chul
YC
Lee
Kwang Youl
KY
Jeong
Hye Gwang
HG
D000469:Alkaline Phosphatase / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism*; D004247:DNA / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D010006:Osteoblasts / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects; D018517:Plant Roots / Q000737:chemistry; D010957:Plasmids; D031238:Platycodon / Q000737:chemistry*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000235:genetics*
D050659:Core Binding Factor Alpha 1 Subunit; C493717:Runx2 protein, rat; D012503:Saponins; D012313:RNA; D004247:DNA; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000469:Alkaline Phosphatase