Pigment epithelium derived factor (PEDF) prevents methyl methacrylate monomer-induced cytotoxicity in H9c2 cells

Acrylic bone cements are currently the most frequently and extensively used materials in orthopedic implant treatment. However, adverse effects have been described of acrylic bone cement on the cardiovascular system. In the present study, we examined the cytotoxicity of bone cement ingredient methyl methacrylate (MMA) to cardiomyocytes 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, MMA at low concentrations (30-90 mmol/L) caused apoptosis. Pretreatment of PEDF prevented MMA-induced cytotoxicity. In addition, PEDF enhanced total superoxide dismutase activities, and decreased MMA-induced production of malonaldehyde. Furthermore, MMA-induced downregulation of Akt activity was suppressed by PEDF. PEDF also increased the levels of peroxisome proliferator activated receptor gamma (PPAR g) and lysophosphatidic acids (LPA) through PEDF receptor. These results indicated that PEDF inhibited MMA-induced cytotoxicity through attenuating oxidative stress, activating the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and/or PEDF receptor-LPA-PPAR g pathways in H9c2 cells. PEDF may be explored as a candidate therapeutic agent for alleviating bone cement implantation syndrome during orthopedic surgery.