Ebselen restores peri-implantitis-induced osteogenic inhibition via suppressing BMSCs ferroptosis

It is hard to reconstruct bone defects in peri-implantitis due to osteogenesis inhibited by excessive reactive oxygen species (ROS). Ferroptosis, a recently identified regulated cell death characterized by iron- and ROS- dependent lipid peroxidation, provides us with a new explanation. Our study aims to explore whether ferroptosis is involved in peri-implantitis-inhibited osteogenesis and confirm ebselen, an antioxidant with glutathione peroxidase (GPx)-like activity, could inhibit ferroptosis and promote osteogenesis in peri-implantitis. In this study, we used LPS to mimic the microenvironment of peri-implantitis. The osteogenic differentiation of bone-marrow-derived mesenchymal stem cells (BMSCs) was assessed by alkaline phosphatase (ALP), Alizarin Red S, and mRNA and protein expression of osteogenic-related markers. Ferroptosis index analysis included iron metabolism, ROS production, lipid peroxidation and mitochondrial morphological changes. Iron overload, reduced antioxidant capability, excessive ROS, lipid peroxidation and the characteristic mitochondrial morphological changes of ferroptosis were observed in LPS-treated BMSCs, and adding Ferrostatin-1 (Fer-1) restored the inhibitory effect of ferroptosis on osteogenic differentiation of BMSCs. Furthermore, ebselen ameliorated LPS-induced ferroptosis and osteogenic inhibition, which were reversed by erastin. Our results demonstrated that ferroptosis is involved in osteogenic inhibition in peri-implantitis and ebselen could attenuate osteogenic dysfunction of BMSCs via inhibiting ferroptosis.