Strontium Ameliorates Glucocorticoid Inhibition of Osteogenesis Via the ERK Signaling Pathway.

Glucocorticoid (GC) has been widely used in clinical work due to its anti-inflammatory and immune-inhibitory properties. However, long-term or high-dose administration is associated with side effects, such as GC-induced osteoporosis (GIOP), which causes great pain for and poses a heavy financial burden on patients. We sought to investigate the potential effects of strontium on GIOP and further explore its underlying mechanisms, including its reversal of the inhibitory effect of GC on osteogenesis of bone marrow-derived mesenchymal stem cells (BMSCs). We incubated BMSCs with Dexamethasone (DEX) in combination with or without strontium and then measured osteogenic and adipogenic gene expression levels by RT-qPCR and Western blot. We added a specific ERK signaling pathway inhibitor, U0126, to evaluate the involvement of that pathway. Strontium promoted osteogenic differentiation and matrix mineralization in DEX-treated BMSCs, accompanied by upregulation of RUNX2, Osx, ALP, BSP, COL1A1, and OCN. DEX blocked the expression of several osteogenesis-related marker genes by activating the ERK signaling pathway. U0126 attenuated the suppression of osteogenesis in DEX-treated BMSCs. These results suggested that strontium could enhance osteogenic differentiation and matrix mineralization by counteracting DEX's inhibitory effect on osteogenesis via the ERK signaling pathway. Therefore, strontium might be a promising therapeutic agent for GIOP.