Stress to endoplasmic reticulum of mouse osteoblasts induces apoptosis and transcriptional activation for bone remodeling.
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.
Hamamura
Kazunori
K
Department of Biomedical Engineering, and Anatomy and Cell Biology, Indiana University Purdue University Indianapolis, Fesler Hall 115, 1120 South Drive, Indianapolis, IN 46202, USA.
Yokota
Hiroki
H
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
C081452:Atf4 protein, mouse; D015852:Eukaryotic Initiation Factor-2; D014415:Tunicamycin; D051701:Activating Transcription Factor 4; D019284:Thapsigargin; D002118:Calcium