Ginsenoside Rh2(S) induces the differentiation and mineralization of osteoblastic MC3T3-E1 cells through activation of PKD and p38 MAPK pathways.
As part of the search for biologically active anti-osteoporotic agents that enhance differentiation and mineralization of osteoblastic MC3T3-E1 cells, we identified the ginsenoside Rh2(S), which is an active component in ginseng. Rh2(S) stimulates osteoblastic differentiation and mineralization, as manifested by the up-regulation of differentiation markers (alkaline phosphatase and osteogenic genes) and Alizarin Red staining, respectively. Rh2(S) activates p38 mitogen-activated protein kinase (MAPK) in time- and concentration-dependent manners, and Rh2(S)-induced differentiation and mineralization of osteoblastic cells were totally inhibited in the presence of the p38 MAPK inhibitor, SB203580. In addition, pretreatment with Go6976, a protein kinase D (PKD) inhibitor, significantly reversed the Rh2(S)-induced p38 MAPK activation, indicating that PKD might be an upstream kinase for p38 MAPK in MC3T3-E1 cells. Taken together, these results suggest that Rh2(S) induces the differentiation and mineralization of MC3T3-E1 cells through activation of PKD/p38 MAPK signaling pathways, and these findings provide a molecular basis for the osteogenic effect of Rh2(S).
Department of Life and Nanopharmaceutical Science, Graduate School of Kyung Hee University, Seoul, Korea.
Do Yeon
DY
Kim
Mi Song
MS
Jung
Young Guk
YG
Park
Hai Dan
HD
Yuan
Hai Yan
HY
Quan
Sung Hyun
SH
Chung
D016475:3T3 Cells; D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D036145:Ginsenosides; C089212:protein kinase D; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases