Increase in epidermal growth factor receptor protein induced in osteoblastic cells after exposure to flow of culture media.
To investigate how bone cells respond to mechanical stimuli, we subjected osteoblastic cells to fluid flow. We and others already reported that in a culture system of osteoblast-like cells, ERK1/2, Shc, and other proteins were tyrosine-phosphorylated by medium flow and the early response gene, egr-1 or c-fos mRNA, increased. These are the same as events found after stimulation by various growth factors. Moreover, because there were also reports suggesting that growth factor signaling is involved in the responses to mechanical stimuli, we examined the change in epidermal growth factor (EGF) receptor in the cells exposed to medium flow. The results demonstrated that EGF receptor protein increased after exposure to medium flow. This increase did not occur without serum in media, and the addition of EGF restored it. Furthermore, leupeptin blocked this increase. These results suggest that degradation of EGF-occupied EGF receptor by leupeptin-sensitive protease(s) in endosomes decreased with exposure to medium flow. This was presumed to participate, at least in part, in signaling of fluid flow.
Ogata
Toshiko
T
Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 3-10 Kandasurugadai 2-chome, Chiyodaku, Tokyo 101-0062, Japan. oga.mph@mri.tmd.ac.jp
D001846:Bone Development / Q000187:drug effects / Q000502:physiology*; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000187:drug effects / Q000378:metabolism*; D010812:Physical Stimulation; D011480:Protease Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013314:Stress, Mechanical; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
D017077:Culture Media, Conditioned; D007976:Leupeptins; D011480:Protease Inhibitors; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D010447:Peptide Hydrolases; C032854:leupeptin