RESUMEN
Glucocorticoid-Induced Osteoporosis (GIOP) is a prevalent clinical complication caused by large dose administration of glucocorticoids, such as Dexamethasone (Dex) and Prednisone. GIOP may lead to fractures and even Osteonecrosis of the Femoral Head (ONFH). It has been reported that glucocorticoids inhibit osteogenesis via the suppression of osteogenic differentiation in Mesenchymal Stem Cells (MSCs), but the precise mechanism underlying this suppression awaits further investigation. Meanwhile, novel and efficacious therapies are recommended to cope with GIOP. In this study, we demonstrated that Dex had the inhibitory effect on Bone Morphogenetic Protein 9 (BMP9)-induced ALP activities and matrix mineralization in Mouse Embryonic Fibroblasts (MEFs). In addition, the study confirmed that Dex decreased the expression of osteogenic markers such as Runx2 and OPN. However, the inhibitory effect of Dex on these osteogenic markers can be reversed when combined with insulin-like growth factor 1 (IGF-1). Regarding the inhibitory mechanism, we found that the level of AKT and p-AKT can be decreased by Dex and that Ly294002, the PI3K inhibitor, can block the reversal effect of IGF-1. Moreover, the knockdown or inhibition of COX-2 produced similar results to those of Ly294002. Our findings indicated that IGF-1 may reverse the osteogenic inhibitory effect of Dex via PI3K/AKT pathway, which may be associated with the up-regulation of COX-2. This study may provide new clinical management strategy for GIOP cases.
Asunto(s)
Dexametasona/efectos adversos , Fibroblastos/efectos de los fármacos , Glucocorticoides/efectos adversos , Factor 2 de Diferenciación de Crecimiento/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Osteogénesis/efectos de los fármacos , Animales , Línea Celular , Células Cultivadas , Ciclooxigenasa 2/metabolismo , Femenino , Fibroblastos/citología , Fibroblastos/metabolismo , Humanos , Ratones , Ratones Desnudos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
<p><b>OBJECTIVE</b>To investigate the effect of Lishi No.5 formula on the growth of human neuroblastoma cell line SY5Y and find out the most effective drug dose.</p><p><b>METHOD</b>SY5Y cells were administrated by Lishi No.5 formula in different concentration. MTT metabolic rate was measured as the cell survival rate, then the dose-effect curve was made. LDH leakage rate, axonal length and area of cell body were used as the indicators.</p><p><b>RESULT</b>In 0.125-0.75 g x L(-1) Lishi No. 5 formula could increase the cell survival rate and MTT metabolic rate, decreased LDH leakage rate, and enhance axonal length and area of cell body, compared with control group.</p><p><b>CONCLUSION</b>Lishi No.5 formula has the neurotrophic effect and can induce the survival of neuron.</p>