title: Heat-shock-induced three-dimensional-like proliferation of mouse fibroblasts mediated by hydroxyapatite.
abstract: The aim of the present study was to determine both the minimal and the optimal conditions under which heat treatment is effective for enhancing 3D (three-dimensional)-like cell proliferation. C3H10T1/2 mouse fibroblasts were cultured with hydroxyapatite granules for 10 weeks after heat treatment at 40, 41.5, 43, 44 or 45 degrees C for 2, 10, 15, 20, 30, 45, 60, 90, 180 and 360 min. Then minimal and optimal conditions of temperature and duration of heat treatment for induction of 3D-like proliferation of cells were determined. The minimal conditions of heat treatment to induce 3D-like proliferation were 43 degrees C for 2 min and the optimal conditions were 43 degrees C for 10 min. The mean rates of formation of 3D-like proliferation patterns by cells heat-treated at 43 degrees C for 2 and 10 min were significantly higher (1.7- and 3.7-fold respectively) than that by untreated cells (P<0.05). We also observed significantly greater effects of heat treatment on 3D-like proliferation at 40 degrees C for 90 or 180 min and at 41.5 degrees C for 15 min and 44 degrees C for 10 min. We found that apoptosis had occurred in 7.5 and 87.0% of the cells at 1 week after heat treatment at 43 degrees C for 10 min and 30 min respectively. Western-blot analysis demonstrated that phosphorylation of p38 MAPK (mitogen-activated protein kinase) was markedly increased by heat treatment at 43 degrees C for 10 min. These findings suggest that activation of p38 MAPK by heat shock is associated with 3D-like cell proliferation. The results of the present study should be useful for further studies aimed at elucidation of the physiological mechanisms underlying thermotherapy and hyperthermia.
authors.affiliation: Department of Physical Therapy, School of Health Science, KIBI International University, 8 Iga-machi Takahashi City, Okayama 716-8508, Japan. hiragami@kiui.ac.jp
authors.forename: Fukumi
authors.initials: F
authors.lastname: Hiragami
authors.forename: Junichi
authors.initials: J
authors.lastname: Akiyama
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Koike
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kano
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D017886:Durapatite; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology*; D018869:Heat-Shock Response; D006358:Hot Temperature; D020287:In Situ Nick-End Labeling; D051379:Mice; D008809:Mice, Inbred C3H; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017886:Durapatite; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases