Reversal Mechanism Of All-trans Retinoic Acid In Dex-inhibited Osteogenic Differentiation On MSCs

Glucocorticoid-Induced Osteoporosis(GIOP)is one of the main causes of secondary osteoporosis in adolescents.Dexamethasone(Dex)is the earliest and most widely used clinical glucocorticoid.It has a close relationship with the occurrence and development of GIOP.At present,there is still a lack of effective prevention and treatment methods in clinical practice.In order to find an efficient and stable treatment method,this experiment used Western blot,Alkaline Phosphatase(ALP)staining and other methods,Bone Morphogenetic Protein 9(BMP9)and C3H10T1/2 Mesenchymal Stem Cells(MSCs)were used to construct the bone model to explore the effect of all-trans retinoic acid(ATRA)on Dexamethasone's inhibition of osteogenic differentiation,and related molecular mechanisms.The results showed that in C3H10T1/2 cells,Dex could inhibit BMP9-induced osteogenic differentiation,down-regulated the expression of RUNX2 and OPN protein levels;ATRA could promote BMP9-induced osteogenic differentiation and reverse the inhibitory effect of Dex on osteogenic differentiation;Meanwhile,Dex could promote the expression of SOST,inhibited the phosphorylation of GSK-3? and theprotein expression of ?-catenin;ATRA showed opposite to the above regulation effects of Dex,and could promote the phosphorylation of AKT;SOST could inhibit the phosphorylation of GSK-3?,Phosphorylation of AKT and expression of ?-catenin.The above results indicate that ATRA can reverse the inhibitory effect of Dex on osteogenic differentiation.This mechanism may be achieved by inhibiting the expression of SOST and positively regulating the Wnt / ?-catenin pathway;at the same time,ATRA may also positively regulate AKT / GSK-3? / ?-catenin promotes osteogenic differentiation,but the specific mechanism research is not yet complete.