Enhancement of hydroxyapatite-mediated three-dimensional-like proliferation of mouse fibroblasts by heat treatment: effects of heat shock-induced p38 MAPK pathway.

Regulation of the biocompatibility of compositional hydroxyapatite (HA) with cells is affected by various environmental factors. The aim of this study was to determine whether the p38 mitogen-activated protein kinase (MAPK) pathway has a key role in enhancement of HA-mediated three-dimensional (3D)-like proliferation of mouse fibroblasts after heat treatment. C3H10T1/2 mouse fibroblasts were cultured with HA granules for 10 weeks after heat treatment at 44 degrees C for 5, 10, 20, and 30 min. The mean rate of formation of 3D-like proliferation patterns by cells heat treated for 20 min was only 2.1-fold higher than that by untreated cells, but the mean rates of formation of 3D-like proliferation patterns by cells heat treated for 5 and 10 min were significantly higher (3.7- and 3.3-fold higher, respectively) than that by untreated cells (p < 0.01). Western blot analysis demonstrated that phosphorylation of p38 MAPK was markedly increased by heat treatment at 44 degrees C for 5 and 10 min. In addition, the activation of heat shock-induced p38 MAPK was markedly reduced by treatment at 44 degrees C for 30 min. We concluded that 3D-like proliferation of heat-treated cells was induced by activation of p38 MAPK. The results of this study should be useful for further studies aimed at elucidation of regulation of the biocompatibility of compositional HA with cells. (c) 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005.