Glucocorticoid dose determines osteocyte cell fate

Junjing Jia, Wei Yao, Min Guan, Weiwei Dai, Mohammad Shahnazari, Rekha Kar, Lynda Bonewald, Jean X. Jiang, Nancy E Lane

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

In response to cellular insult, several pathways can be activated, including necrosis, apoptosis, and autophagy. Because glucocorticoids (GCs) have been shown to induce both osteocyte apoptosis and autophagy, we sought to determine whether osteocyte cell fate in the presence of GCs was dose dependent by performing in vivo and in vitro studies. Male Swiss-Webster mice were treated with slow-release prednisolone pellets at 1.4, 2.8, and 5.6 mg/kg/d for 28 d. An osteocyte cell line, MLO-Y4 cells, was treated with various doses of dexamethasone. We found that GC treatments dose dependently decreased activation of antioxidant-, autophagy-, and antiapoptosis-focused RT-PCR gene pathways in mouse cortical bone. The activation of antioxidant genes was correlated with autophagy gene expression after the GC treatments. The presence of osteocyte autophagy, as detected by immunostaining for LC3, increased ∼50% at the distal femur cortical bone region but not at trabecular bone region at the 1.4 and 2.8 mg/kg/d GC dose levels. The number of apoptotic osteocytes was increased at the cortical bone region by ∼40% initially observed at the 2.8 mg/kg/d dose level. In addition, the presence of the osteocyte autophagy was associated with an increased protein level of cathepsin K in vitro after the GC treatments. In summary, we found that GC treatment dose-dependently decreased antioxidant gene expression, with lower GC doses activating autophagy, whereas a higher dose increased apoptosis. These data suggest that autophagy may provide a mechanism for osteocytes to survive the stress after GC exposure and provide further insight into how GCs alter bone cell fate.

Original languageEnglish (US)
Pages (from-to)3366-3376
Number of pages11
JournalFASEB Journal
Volume25
Issue number10
DOIs
StatePublished - Oct 2011

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Keywords

  • Antioxidant
  • Apoptosis
  • Autophagy
  • LC3
  • MLO-Y4 cell
  • Osteoporosis

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Jia, J., Yao, W., Guan, M., Dai, W., Shahnazari, M., Kar, R., Bonewald, L., Jiang, J. X., & Lane, N. E. (2011). Glucocorticoid dose determines osteocyte cell fate. FASEB Journal, 25(10), 3366-3376. https://doi.org/10.1096/fj.11-182519