Osteocytic cells exposed to titanium particles increase sclerostin expression and inhibit osteoblastic cell differentiation mostly via direct cell-to-cell contact

The mechanism underlying induction of periprosthetic osteolysis by wear particles remains unclear. In this study, cultured MLO-Y4 osteocytic cells were exposed to different concentrations of titanium (Ti) particles. The results showed that Ti particles increased expression of the osteocytic marker SOST/sclerostin in a dose-dependent manner, accelerated apoptosis of MLO-Y4 cells, increased the expression of IL-6, TNF-alpha and connexin 43. SOST silence alleviated the increase of MLO-Y4 cells apoptosis, decreased the expression of IL-6, TNF-alpha and connexin 43 caused by Ti particles. The different co-culture systems of MLO-Y4 cells with MC3T3-E1 osteoblastic cells were further used to observe the effects of osteocytic cells' changes induced by Ti particles on osteoblastic cells. MLO-Y4 cells treated with Ti particles inhibited dramatically differentiation of MC3T3-E1 cells mostly through direct cell-to-cell contact. SOST silence attenuated the inhibition effects of Ti-induced MLO-Y4 on MC3T3-E1 osteoblastic differentiation, which ALP level and mineralization of MC3T3-E1 cells increased and the expression of ALP, OCN and Runx2 increased compared to the Ti-treated group. Taken together, Ti particles had negative effects on MLO-Y4 cells and the impact of Ti particles on osteocytic cells was extensive, which may further inhibit osteoblastic differentiation mostly through intercellular contact directly. SOST/sclerostin plays an important role in the process of mutual cell interaction. These findings may help to understand the effect of osteocytes in wear particle-induced osteolysis.

Automated summary

This study investigated the effects of titanium particles on MLO-Y4 osteocytic cells and their impact on osteoblastic cells. The results showed that titanium particles increased osteocytic marker expression, apoptosis, and the expression of inflammatory factors. The particles also inhibited the differentiation of osteoblastic cells through direct cell-to-cell contact. Silencing of SOST/sclerostin attenuated these effects. These findings highlight the extensive impact of titanium particles on osteocytic cells and the importance of SOST/sclerostin in cell interaction.