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Involvement of small G protein RhoB in the regulation of proliferation, adhesion and migration by dexamethasone in

Fei Diao1, Kangyao Chen2,3, Yan Wang1

  • 1Department of Pathophysiology, Second Military Medical University, Shanghai, China.

Plos One
|March 22, 2017
PubMed

Insights

Glucocorticoids (GCs) impair bone health by affecting osteoblasts. This study reveals that dexamethasone (Dex) increases RhoB expression, impacting osteoblast growth and migration, contributing to GC-induced bone remodeling issues.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Endocrinology

Background:

  • Long-term glucocorticoid (GC) therapy causes bone loss and impairs fracture healing by disrupting osteoblast function.
  • The precise molecular mechanisms underlying GC effects on osteoblasts remain incompletely understood.

Purpose of the Study:

  • To investigate the role of the small G protein RhoB in the cellular responses of osteoblasts to dexamethasone (Dex).
  • To elucidate the signaling pathways involved in Dex-induced RhoB expression and its functional consequences in osteoblasts.

Main Methods:

  • Utilized MG-63 osteosarcoma cell line, a model for osteoblast-like cells.
  • Assessed RhoB mRNA and protein expression following Dex treatment.
  • Employed RNA interference and overexpression techniques to manipulate RhoB levels.
  • Investigated the involvement of PI-3K/Akt and p38 MAPK signaling pathways.
  • Evaluated effects on cell proliferation, differentiation, adhesion, and migration.

Main Results:

  • Dexamethasone (Dex) significantly increased RhoB mRNA and protein expression in MG-63 cells.
  • Dex-induced RhoB upregulation occurred at the posttranscriptional level, enhancing mRNA stability via PI-3K/Akt and p38 MAPK pathways.
  • Overexpression of RhoB mimicked Dex-induced growth inhibition and affected cell adhesion and migration.
  • RhoB knockdown partially reversed Dex-induced effects on cell adhesion and migration, but not growth inhibition.

Conclusions:

  • RhoB is a key mediator of dexamethasone's pathological effects on osteoblast proliferation, adhesion, and migration.
  • RhoB plays a significant role in the adverse skeletal effects of glucocorticoids, contributing to abnormal bone remodeling.

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