Related Experiment Video

Updated: Jul 9, 2026

Tension-Free Weight-Bearing Model of Steroid-Induced Osteonecrosis of Femoral Head in Rats
05:55

Tension-Free Weight-Bearing Model of Steroid-Induced Osteonecrosis of Femoral Head in Rats

Published on: September 27, 2024

Regulation of bim in glucocorticoid-mediated osteoblast apoptosis

B Espina1, M Liang, R G G Russell

  • 1The Botnar Research Centre, Oxford Institute of Musculoskeletal Sciences, Nuffield Department of Orthopaedic Surgery, Oxford, UK. mbespina@humv.es

Journal of Cellular Physiology
|December 8, 2007
PubMed

Insights

Glucocorticoids induce osteoblast apoptosis via the pro-apoptotic protein Bim. Targeting Bim may prevent GC-induced bone loss and related side effects.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Endocrinology

Background:

  • Glucocorticoids (GCs) induce osteoblast apoptosis, a significant side effect with unclear molecular mechanisms.
  • Understanding GC-induced osteoblast apoptosis is crucial for preventing GC-related bone complications.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying glucocorticoid-induced osteoblast apoptosis.
  • To identify novel therapeutic targets for preventing GC-induced bone loss.

Main Methods:

  • Dexamethasone (Dex) treatment of murine osteoblasts (MBA-15.4) and primary human bone marrow stromal cells.
  • Analysis of Bim protein and mRNA expression, including effects of cycloheximide, RU486, and MG132.
  • Gene silencing using small interfering RNA (siRNA) targeting Bim and Bax.

Main Results:

  • Dexamethasone treatment upregulated Bim protein and mRNA in a dose- and time-dependent manner.
  • Bim upregulation involved transcriptional regulation via the glucocorticoid receptor and post-translational regulation by the proteasome.
  • Silencing Bim or Bax expression reduced dexamethasone-induced osteoblast apoptosis.

Conclusions:

  • Bim is a key regulator of glucocorticoid-induced osteoblast apoptosis.
  • Bim represents a potential therapeutic target for mitigating the adverse effects of glucocorticoid therapy on bone health.

Related Concept Videos

Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Osteoclasts in Bone Remodeling01:31

Osteoclasts in Bone Remodeling

Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during bone...
Bone Remodeling01:40

Bone Remodeling

Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...