Effects of deferoxamine on the osteogenic differentiation of human periodontal ligament cells

Hypoxia regulates a number of cell biological processes, including cell survival, development and differentiation. Deferoxamine (DFO), an oral chelator for blood transfusion patients, has been demonstrated to induce hypoxia and is frequently used as a hypoxia-mimicking agent. The purpose of the present study was to investigate the influence of DFO on the proliferation, migration and osteogenic differentiation of human periodontal ligament cells (hPDLCs). The effects of DFO on hPDLC viability and migration were measured using an MTT and wound healing assay. To characterize the hypoxia microenvironment, the expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) in hPDLCs treated with DFO was quantified using the reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the osteogenic differentiation potential of DFO was determined by RT-qPCR of the mRNA of osteogenic markers ( runt-related transcription factor 2 [Runx-2], osteopontin [OPN] and collagen type I [Col-1]). The alkaline phosphatase activity and mineral deposition were analyzed using alizarin red S staining. The MTT and wound healing assays demonstrated that low-concentrations of DFO had little impact on hPDLC viability and migration 48 h into the treatment. DFO upregulated the expression of hPDLC genes specific for osteogenic differentiation: HIF-1a, Runx-2, OPN and Col-1. Furthermore, formation of mineralized nodules was enhanced by DFO. The present study suggests that DFO provided favorable culture conditions to promote the osteogenic differentiation and mineralization of hPDLCs. The mechanism underlying these alterations remains to be elucidated.