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Updated: Jul 16, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Role of mitogen-activated protein kinase (MAPK) in troglitazone-induced osteoblastic cell death

Ju Young Jung1, Chong Il Yoo, Hui Taek Kim

  • 1Department of Orthopedic Surgery, College of Medicine, Pusan National University, Pusan, Republic of Korea.

Toxicology
|March 17, 2007
PubMed

Insights

Troglitazone induces osteoblast cell death through apoptosis. This mechanism involves caspase activation, suppressed ERK, and increased p38 signaling, independent of reactive oxygen species.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Troglitazone, a PPARgamma agonist, is known to cause cell death.
  • The precise mechanism of troglitazone-induced cell death is not fully understood.
  • Osteoblast cell death is critical for bone remodeling and homeostasis.

Purpose of the Study:

  • To investigate the effects of troglitazone on cell death in MC3T3-E1 osteoblast cells.
  • To elucidate the underlying molecular mechanisms of troglitazone-induced apoptosis.
  • To determine the role of signaling pathways and reactive oxygen species in troglitazone cytotoxicity.

Main Methods:

  • MC3T3-E1 cells were treated with varying concentrations and durations of troglitazone.
  • Cell viability was assessed using standard assays.
  • Apoptosis, reactive oxygen species (ROS) generation, and mitochondrial membrane potential were measured.
  • Western blotting was used to analyze the activation of ERK and p38 pathways.
  • Inhibitors for PPARgamma, ERK, p38, and caspase-3 were employed.

Main Results:

  • Troglitazone dose-dependently decreased cell viability and induced apoptosis in MC3T3-E1 cells.
  • ROS generation was observed but did not mediate troglitazone-induced cell death.
  • Troglitazone-induced cell death was blocked by PPARgamma antagonist GW9662.
  • Troglitazone inhibited ERK activation and stimulated p38 activation.
  • Inhibition of ERK exacerbated cell death, while p38 inhibition and caspase-3 inhibition prevented it.
  • Mitochondrial membrane potential depolarization was observed and blocked by p38 and PPARgamma inhibitors.

Conclusions:

  • Troglitazone induces apoptosis in osteoblasts via a caspase-dependent pathway.
  • The mechanism involves the down-regulation of ERK and up-regulation of p38 signaling.
  • PPARgamma activation is essential for troglitazone-induced cell death.
  • ROS are not the primary mediators of troglitazone cytotoxicity in this model.

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