Abstract
OBJECTIVE: To evaluate the effect of zoledronate acid (ZA) on the proliferation and osteogenic differentiation of rat mesenchymal stem cells (BMSCs). METHODS: The BMSCs isolated from the SD rats were cultured with different concentrations of ZA (1, 5, 10, and 20 μmol·L), and the contro1 group received the same volume of culture medium but without ZA. Cell counting kit-8 was used to detect proliferation activity in each group. Alkaline phosphatase (ALP) staining and alizarin red staining were used to detect the osteogenic differentiation ability in each group. The gene expression levels of ALP, bone morphogenetic protein-2 (BMP-2), typeⅠcollagenase (COL-Ⅰ), runt-related transcription factor-2 (Runx-2), zinc finger structure transcription factor (Osx), osteocalcin (OCN), and osteopontin (OPN) were evaluated by real-time quantitative polymerase chain reaction (qRT-PCR). RESULTS: Zoledronate at 1 μmol·L⁻¹ concentration had no effect on the proliferation and osteogenic differentiation of BMSCs. No significant difference was observed between this group and the control group (P>0.05). When the ZA concentration was more than 1 μmol·L⁻¹, ZA inhibited the proliferation and osteogenic differentiation of BMSCs, and the effect was concentration dependent. The difference between each group and the control group was statistically significant (P<0.05). At ZA concentration of 5 μmol·L⁻¹, ZA enhanced the expression of ALP, BMP-2, COL-Ⅰ, Runx-2, Osx, OCN, and OPN (P<0.05). However, at ZA concentration of more than 5 μmol·L⁻¹, the expression levels of osteogenicrelated genes in each group was lower than those of the control group (P<0.05). CONCLUSIONS: Low ZA concentration has no effect on the proliferation and osteogenic differentiation of BMSCs. ZA at 5 μmol·L⁻¹ concentration inhibits the proliferation but promotes the osteogenic differentiation of BMSCs. High ZA concentration inhibits the proliferation and osteogenic differentiation of BMSCs.