Si Inhibited Osteoclastogenesis: The Role of Fe and the Fenton Reaction.

Abstract

Soluble silicate species (Si) released from bioceramics have been reported to enhance bone regeneration and regulate bone remodeling, but their cellular mechanisms remain unclear. Here, we show that Si inhibited osteoclast (OC) formation and resorption (as determined by OC number, TRAP-5b expression, and volumetric resorption) in a concentration-dependent manner, in both primary OCs and an osteoclastic subclone of the RAW264.7 cell-line (p<0.001). We propose that Si‑mediated inhibition may be mediated via reduced reactive oxygen species (ROS) availability, due to iron‑silicate (Fe-O-Si) interactions. Biochemical assays demonstrated that Si decreased the availability of ROS, and decreased intracellular ROS concentrations in OCs, but only in the presence of Fe. Furthermore, Si-inhibited OC formation is restored by the addition of 10µM Fe (P<0.001). Fe-Si interactions were demonstrated by a reduction in Si and Fe concentrations (P<0.001) in solution (ICP-OES) and by Si─O─Fe bonds observed in precipitates (ATR-FTIR). These results suggest that that Si may inhibit OC activity by regulation of the Fenton reaction. Understanding the intracellular mechanisms of how Si interacts with OCs allows the development of new Si-releasing materials (e.g., bioactive glasses or bioceramics) with controlled release of Si to regulate osteoclastogenesis.