Titanium particles employed Mettl3-mediated RNA methylation for osteolysis

Peri-prosthetic osteolysis (PPO) induced by wear titanium particles has become the primary cause of titanium prosthesis failure and revision surgery.Still, the molecular mechanisms have not been fully revealed. Results revealed that titanium particles exhibited osteogenic inhibition and proinflammatory activities, accompanied by the down-regulated expression of Mettl3.The Mettl3 knockdown and overexpression experiments verified the upstream regulating role of Mettl3. In terms of mechanisms, titanium particles mediated the methylation of two inhibitory molecules, leading to the osteogenic inhibition. Similarly, particles triggered the activation of NOD1 signaling pathway through methylation regulation and the subsequent activation of MAPK and NF-κB pathways. Collectively, titanium particles employed Mettl3 as an upstream regulation molecule to achieve osteogenic inhibition and pro-inflammatory reaction.