| Abstract: | Acrylic bone cements are currently the most frequently and extensively used materials in orthopedic implanttreatment. However, adverse effects have been described of acrylic bone cement on the cardiovascular system. In thepresent study, we examined the cytotoxicity of bone cement ingredient methyl methacrylate (MMA) tocardiomyocytes and the potential detoxifying effect of pigment epithelium-derived factor (PEDF) in H9c2 cells.We found that high concentration of MMA ( > 120 mmol/L) led to necrotic cell death in H9c2 cells. However, MMAat low concentrations (30-90 mmol/L) caused apoptosis. Pretreatment of PEDF prevented MMA-inducedcytotoxicity. In addition, PEDF enhanced total superoxide dismutase activities, and decreased MMA-inducedproduction of malonaldehyde. Furthermore, MMA-induced downregulation of Akt activity was suppressed by PEDF.PEDF also increased the levels of peroxisome proliferator activated receptor gamma (PPARg) and lysophosphatidicacids (LPA) through PEDF receptor. These results indicated that PEDF inhibited MMA-induced cytotoxicity throughattenuating oxidative stress, activating the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and/or PEDF receptorLPA-PPARg pathways in H9c2 cells. PEDF may be explored as a candidate therapeutic agent for alleviating bonecement implantation syndrome during orthopedic surgery. |
