The role of TGF-β1/Smad3 signaling pathway and oxidative stress in the inhibition of osteoblast mineralization by copper chloride

To explore the relationship of oxidative stress and TGF-beta 1/Smad3 pathway in the inhibition of osteoblast mineralization by copper chloride (CuCl2), the osteoblasts were treated with CuCl2 (0, 50 mu M, 100 mu M, 150 mu M CuCl2 5H(2)O) for 24 h. We found that Cu impaired the osteoblast structure, inhibited the glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities, alkaline phosphatase (ALP) content, mRNA expression of collagen I (COL-I), osteocalcin (OCN), insulin-like growth factor I (IGF-I), bone morphogenetic protein-2 (BMP-2), transforming growth factor beta 1 (TGF-beta 1) and core-binding factor alpha 1 (Cbf alpha 1), promoted the reactive oxygen species (ROS) production, inactivated the TGF-beta 1/Smad3 pathway. It indicates that the inactivated TGF-beta 1/Smad3 pathway leads to osteoblast impairment by CuCl2. It will contribute to clarify the influence of CuCl2 on the osteoblast mineralization.