osteogenesis such as alkaline phosphatase, core-binding factor a1, and bone sialoprotein while depressing the mRNA levels of PPAR 2, a key transcription factor that has been Luteolin shown to inhibit osteogenesis [43]. Osteoblasts and adipocytes differentiate from a common precursor, the pluripotent mesenchymal stem cells in bone marrow and regulation of PPAR 2 activity has been shown to control the fate of these cells towards osteogenesis or adipogenesis. Suppression of PPAR 2 activity was associated with enhanced osteogenesis . Our findings indicate that attenuate PPAR 2 activity of bone marrow stromal cells is the potential mechanism of Panax notoginseng saponins stimulated the osteogenesis. The effects of Panax notoginseng saponins on these osteogenesis-associated genes could be through modulating the MAPK signaling pathways. MAPK signaling pathways are important for osteogenesis [30, 45-47].
Inhibitor of ERK, PD98059, could significantly inhibit osteogenic differentiation of bone Fesoterodine marrow stromal cells and caused these cells to develop into fully mature adipocytes . Alendronate was found to stimulate osteogenic differentiation and inhibit adipogenic differentiation of bone marrow stromal cells by the ERK and JNK signaling pathways . p38 inhibitor, SB203580, remarkably blocked Tigoenin-induced osteogenesis of bone marrow stromal cells [48]. In the present study, we showed that the ERK and p38 MAPK signaling pathways became phosphorylated in bone marrow stromal cells undergoing osteogenic differentiation. Our results further showed that inhibition of the ERK and p38 MAPK signaling pathways attenuated Panax notoginseng saponins-induced phosphorylation of ERK and p38 in bone marrow stromal cells under osteogenic buy Staurosporine induction.
These data indicate that both the ERK and p38 signaling pathways are involved in Panax notoginseng saponins-potentiated osteogenic differentiation of bone marrow stromal cells. It has been reported that ERK can directly result in the phosphorylation of PPAR 2 and reduces the levels of PPAR 2. p38 MAPK plays a negative role in regulating PPAR 2 transcriptional activities[50]; inhibition or disruption of p38 leads to increased PPAR 2 expression and transactivation. We also showed here that inhibition of the ERK and p38 signaling pathways was associated with increased PPAR 2 mRNA transcript levels in bone marrow stromal cells undergoing osteogenic induction in the presence of Panax purchase Glycyrrhizic acid notoginseng saponins. In summary, our study showed that Panax notoginseng saponins potentiated the osteogenic differentiation of bone marrow stromal cells with enhanced mineralization and increased alkaline phosphatase activities of bone marrow stromal cells. We further demonstrated that Panax notoginseng saponins enhanced the phosphorylation of ERK and p38 in bone marrow stromal cells under osteogenic induction.
Our findings shed light on the mechanisms whereby Panax notoginseng saponins potentiate the osteogenesis of bone marrow stromal cells. Acknowledgements A. Conflict of interest: The authors declare that they have no conflict of interest. B. Sources of funding: This study was supported by the China Postdoctoral Science Foundation Cardiac physiology (20090450913), Supported by Medical Scientific Research Foundation of Guangdong Province.