Abstract: Objective To observe the effects of Parmidronate disodium on the biological properties of human bone marrow mesenchymal stem cells (MSCs) to shed a light on the mechanisms underlying the damaging activity of alendronate on bone tissue. Methods Parmidronate disodium at graded doses was added into the culture of human bone marrow MSCs and the culture was maintained for 72 hours, MTT test was used to evaluate the cellular proliferation status. Also, the surface marker profile was observed after culture for one week. MSCs were cultured in the presence of parmidronate disodium (0.5μg/mL) for 2 weeks and the cellular activity of alkaline phosphatase was detected. The total cellular protein content was used as the internal reference. Results The results from MTT assay showed that Parmidronate disodium within a range of concentrations (0.1-10 μg/mL) inhibited human MSC growth in a dose-dependent manner;The lowest effective dose was 1.0μg/mL, and the value of OD490 from MSCs cultured in the presence of Parmidronate disodium for 72 hours was significantly lower than that of the counterparts without the addition of this drug. Flow cytometric analysis showed that parmidronate disodium-treated MSCs expressed homogenously CD44 and CD73 and were negative for CD31 and CD45. Furthermore, the cellular activity of alkaline phosphatase was unchanged after exposure to parmidronate disodium, and it did not take any effect on the differentiation-inducing activity of the standard osteogenic agents. Conclusion Parmidronate disodium could inhibit the proliferation of human bone marrow MSCs, and have not significant effect on their differentiation along osteoblast lineage. The growth inhibitory activity of parmidronate disodium might be one of the mechanisms responsible for its destructive action on bone tissue.

Key words: Parmidronate disodium, Mesenchymal stem cells, Osteoblast differentiation