title: Stress to endoplasmic reticulum of mouse osteoblasts induces apoptosis and transcriptional activation for bone remodeling.
abstract: ATF4 is an essential regulator in osteogenesis as well as in stress responses to the endoplasmic reticulum (ER). We addressed a question: Does ER stress to osteoblasts upregulate ATF4 expression? If so, do they exhibit ATF4-mediated bone remodeling or apoptosis? ER stress, induced by Thapsigargin and tunicamycin, elevated a phosphorylated form of eIF2alpha and ATF4, but the cellular fate depended on treatment duration. The treatment for 1h, for instance, activated Runx2, and type I collagen, while the treatment for 24h induced apoptosis. Our observations suggest that there is a threshold for ER stress and osteoblasts present a bi-phasic pattern of their fate.
authors.affiliation: Department of Biomedical Engineering, and Anatomy and Cell Biology, Indiana University Purdue University Indianapolis, Fesler Hall 115, 1120 South Drive, Indianapolis, IN 46202, USA.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Hamamura
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yokota
mesh_terms: D051701:Activating Transcription Factor 4 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D016723:Bone Remodeling / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D015533:Transcriptional Activation / Q000187:drug effects; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: C081452:Atf4 protein, mouse; D015852:Eukaryotic Initiation Factor-2; D014415:Tunicamycin; D051701:Activating Transcription Factor 4; D019284:Thapsigargin; D002118:Calcium