Wnt, β-catenin

Osteosarcoma cell viability decreases significantly in a concentration- and time-dependent manner at pamidronate concentrations ranging from 100 to 1000 μM, most consistently after 48 and 72 hours' exposure. In treated osteosarcoma cells, the lowest percentage cell viability is 34% (detected after 72 hours' exposure to 1000μM pamidronate). Pamidronate disodium inhibits Wnt and β-catenin signaling, which controls osteogenic differentiation in BMMSCs. Wnt3a, a Wnt and β-catenin signaling activator, reverses the negative effects caused by pamidronate disodium to salvage the osteogenic defect in BMMSCs.

Pamidronic acid can significantly inhibit and even reverse early osteoarthritic subchondral bone loss, thus alleviating the process of cartilaginous degeneration. The mechanisms involved may be associated with the upregulation of OPG expression, and downregulation of RANKL, MMP-9 and TLR-4 expression.