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Stress to endoplasmic reticulum of mouse osteoblasts induces apoptosis and transcriptional activation for bone

Kazunori Hamamura1, Hiroki Yokota

  • 1Department of Biomedical Engineering, and Anatomy and Cell Biology, Indiana University Purdue University Indianapolis, Fesler Hall 115, 1120 South Drive, Indianapolis, IN 46202, USA.

FEBS Letters
|April 10, 2007
PubMed

Insights

Endoplasmic reticulum (ER) stress in osteoblasts upregulates ATF4. Short-term stress promotes bone formation, while prolonged stress induces apoptosis, indicating a threshold for cell fate.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Bone Biology

Background:

  • Activating transcription factor 4 (ATF4) is crucial for osteogenesis and cellular stress responses.
  • The role of endoplasmic reticulum (ER) stress in regulating ATF4 and osteoblast fate remains unclear.

Purpose of the Study:

  • To investigate whether ER stress upregulates ATF4 expression in osteoblasts.
  • To determine if osteoblasts exhibit ATF4-mediated bone remodeling or apoptosis under ER stress.

Main Methods:

  • Osteoblasts were subjected to ER stress using Thapsigargin and tunicamycin.
  • Levels of phosphorylated eIF2alpha and ATF4 were measured.
  • Gene expression of Runx2 and type I collagen was analyzed.
  • Cellular apoptosis was assessed after different treatment durations.

Main Results:

  • ER stress significantly elevated phosphorylated eIF2alpha and ATF4.
  • Short-term ER stress (1h) activated Runx2 and type I collagen, suggesting bone remodeling.
  • Prolonged ER stress (24h) induced apoptosis in osteoblasts.

Conclusions:

  • Osteoblasts exhibit a bi-phasic response to ER stress, dependent on duration.
  • A threshold for ER stress exists, determining whether osteoblasts undergo bone remodeling or apoptosis.
  • ATF4 plays a key role in mediating these differential cellular fates.

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