Abstract
Biodegradable polyphosphoesters (PPEs) are of increasing interest due to their promising biomedical applications. Polyphosphodiesters (PPDEs), formed by polyphosphotriester (PPTE) dealkylation, have bone-targeting properties in vivo and therefore are promising polymer drug candidates for bone disease treatment. However, their effects on osteoblasts are still unclear. This study prepared two polymer structures, poly(methyl ethylene phosphate) (PMP) and poly(ethylene sodium phosphate) (PEP•Na), as PPTE and PPDE models, respectively, and investigated their effects on mouse osteoblastic cell (MC3T3-E1) differentiation. Results showed that PMP is inert toward osteoblast differentiation. In contrast, PEP•Na enhanced alkaline phosphatase (ALP) synthesis, matrix mineralization, and osteoblast-related gene expression. PEP•Na also enhanced Wnt signaling pathway–dependent Alp expression, in addition to its own internalization into the cytosol during 3 days of differentiation culture. These results showed that dealkylated PPEs are a polymer drug candidate for osteoporosis treatment, not only because of their bone-targeting properties but also because of the controllable effects of bone anabolism via osteoblast differentiation enhancement.
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