M.G. Sabbieti and D. Agas contributed equally to this work.
Involvement of p53 in phthalate effects on mouse and rat osteoblasts†
Article first published online: 27 MAR 2009
Copyright © 2009 Wiley-Liss, Inc.
Journal of Cellular Biochemistry
Volume 107, Issue 2, pages 316–327, 15 May 2009
How to Cite
Sabbieti, M.G., Agas, D., Santoni, G., Materazzi, S., Menghi, G. and Marchetti, L. (2009), Involvement of p53 in phthalate effects on mouse and rat osteoblasts. J. Cell. Biochem., 107: 316–327. doi: 10.1002/jcb.22127
- Issue published online: 20 APR 2009
- Article first published online: 27 MAR 2009
- Manuscript Accepted: 10 FEB 2009
- Manuscript Received: 4 AUG 2008
- The Italian Ministry of University and Research (PRIN 2005)
- University of Camerino, Fondazione Carima, Italy
The role of two estrogen-mimicking compounds in regulating osteoblast activities were examined. Previously, our attention was focused on benzyl butyl phthalate (BBP) and di-n-butyl phthalate (DBP) since previous works showed that they enter the cytoplasm, bioaccumulate, modify actin cytoarchitecture and exert mitogenic effects involving microfilament disruption, and nuclear actin and lamin A regulation in Py1a rat osteoblasts. In this study we showed that BBP and DBP cause DNA base lesions both in MT3T3-E1 osteoblasts and in mouse primary calvarial osteoblasts (COBs). In addition, treatment with the above effectors caused an increase of p53 and phospho-p53 (ser-15 and ser-20) as well as an increase of apoptotic proteins with consequent decrease of cell viability. Moreover, treatment with phthalates did not modified p53 and phospho-p53 expression in Py1a rat osteoblasts. It is of relevance that in p53 knockdown mouse osteoblasts a proliferative effect of phthalates, similar to that observed in rat Py1a osteoblasts, was found. In conclusion, our data demonstrated that phthalates induce osteoblast apoptosis, which is, at least in part, mediated by p53 activation, suggesting that the proliferative effects could be due to p53 missing activation or p53 mutation. J. Cell. Biochem. 107: 316–327, 2009. © 2009 Wiley-Liss, Inc.