Reduced Proteoglycan-Rich Layer and Altered Immunotolerance Capacity of C4ST-1-Depleted Bone Marrow Mesenchymal Stem Cells on Titanium Dioxide

Successful osseointegration of a bone and implant directly must be achieved for treatment of a dental implant. However, the mechanism of osseointegration at the molecular level has yet to be fully elucidated. In this study, we focused on the proteoglycans (PGs)-rich layer between titanium dioxide (TiO2) and bone and chondroitin-4-sulfate transferase-1 (C4ST-1) that forms the sugar chain in PGs. Human bone marrow mesenchymal stem cells (hBMSCs) depleted of C4ST-1 were cultured on TiO2, and the interface between hBMSCs and TiO2 was analyzed by transmission electron microscopy. Further, the immunotolerance capacity, cell proliferation, initial attachment, and calcification were analyzed in vitro. At 14 days cultivation, a PGs-rich layer was observed between hBMSCs and TiO2. However, the PGs-rich layer was reduced in C4ST-1-depleted hBMSCs on TiO2. Further, real-time RT-PCR showed that conditioned media increased gene expression levels of M1-macrophage markers in human macrophages. However, C4ST-1 did not affect calcification, cell proliferation, and initial cell attachment on TiO2. These results suggested that C4ST-1 in hBMSCs affected the width of the PGs-rich layer on TiO2 and their immunotolerance capacity.