Strontium ranelate increases osteoblast activity

• Strontium ranelate accelerates the acquisition of the osteoblastic phenotype.
• Strontium ranelate enhances the expression of type I collagen.
• Strontium ranelate promotes the bone-like mineral nodules.

Strontium ranelate (SR) is the first generation of a new class of medication for osteoporosis, which is capable of inducing bone formation and, to a certain extent, inhibiting bone resorption. The aim of this study was to evaluate the in vitro effects of SR on osteoblastic cell cultures. MC3TE-E1 cells were seeded in 24-well plates at a density of 2 × 104 cells/well and exposed to SR at 0.05, 0.1, and 0.5 mM. The following parameters were assayed: 1) Cell proliferation by hemocytometer counting after 24, 48 and 72 h, 2) Cell viability by MTT assay after 24, 48 and 72 h, 3) Type I Collagen and Osteopontin (OPN) quantification by Western Blotting, ELISA, and Real Time PCR after 48 h, 3) Immunolocalization of fibronectin (FN) by epifluorescence, and 4) matrix mineralization by Alizarin Red staining after 14 days. After 24, 48 and 72 h, the cell proliferation and viability were not affected by SR at 0.05 and 0.1 mM (p > 0.05). However, cell cultures exposed to SR at 0.5 mM exhibited a decrease in both cell proliferation and cell viability in all time points assayed (p < 0.05). High levels of protein and mRNA for Type I Collagen and OPN were detected in cultures exposed to SR, particularly at 0.5 mM (p < 0.05). SR allowed the expression of FN in osteoblastic cell cultures as observed by epifluorescence analysis. The mineralized bone-like nodule formation was affected in a concentration-dependent manner by SR, with large bone-like nodules being detected in osteoblastic cell cultures exposed to SR at 0.5 mM. In conclusion, these results suggest that SR can accelerate acquisition of the osteoblastic phenotype, which explains, at least in part, the rebalancing of bone turnover in favor of bone formation.