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.

Low-dose strontium stimulates osteogenesis but high-dose doses cause apoptosis in human adipose-derived stem cells via regulation of the ERK1/2 signaling pathway.

BACKGROUND: Strontium is a widely used anti-osteoporotic agent due to its dual effects on inhibiting bone resorption and stimulating bone formation. Thus, we studied the dose response of strontium on osteo-inductive efficiency in human adipose-derived stem cells (hASCs). METHOD: Qualitative alkaline phosphatase (ALP) staining, quantitative ALP activity, Alizarin Red staining, real-time polymerase chain reaction and Western blot were used to investigate the in vitro effects of a range of strontium concentrations on hASC osteogenesis and associated signaling pathways. RESULTS: In vitro work revealed that strontium (25-500 µM) promoted osteogenic differentiation of hASCs according to ALP activity, extracellular calcium deposition, and expression of osteogenic genes such as runt-related transcription factor 2, ALP, collagen-1, and osteocalcin. However, osteogenic differentiation of hASCs was significantly inhibited with higher doses of strontium (1000-3000 µM). These latter doses of strontium promoted apoptosis, and phosphorylation of ERK1/2 signaling was increased and accompanied by the downregulation of Bcl-2 and increased phosphorylation of BAX. The inhibition of ERK1/2 decreased apoptosis in hASCs. CONCLUSION: Lower concentrations of strontium facilitate osteogenic differentiation of hASCs up to a point; higher doses cause apoptosis of hASCs, with activation of the ERK1/2 signaling pathway contributing to this process.