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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

Advanced glycation end products stimulate osteoblast apoptosis via the MAP kinase and cytosolic apoptotic pathways

Mani Alikhani1, Zoubin Alikhani, Coy Boyd

  • 1Department of Periodontology and Oral Biology, Boston University School of Dental Medicine, Boston, MA 02118, USA.

Bone
|October 27, 2006
PubMed

Insights

Advanced glycation end products (AGEs) significantly increase osteoblastic cell apoptosis, a key factor in impaired bone formation seen in diabetes. This AGEs-induced apoptosis is mediated by the RAGE receptor and specific signaling pathways.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Bone Biology

Background:

  • Diabetes mellitus is associated with impaired bone formation.
  • Advanced glycation end products (AGEs) accumulate in diabetic individuals and are implicated in disease pathogenesis.
  • Osteoblastic cell apoptosis is a potential mechanism contributing to reduced bone formation in diabetes.

Purpose of the Study:

  • To investigate the role of advanced glycation end products (AGEs) in promoting osteoblastic cell apoptosis.
  • To elucidate the molecular mechanisms underlying AGEs-induced osteoblastic cell apoptosis.

Main Methods:

  • In vivo studies using carboxymethyl lysine modified collagen (CML-collagen) injection in mice.
  • In vitro studies using primary cultures of human and rat osteoblastic cells (MC3T3-E1).
  • Assessment of apoptosis, receptor-mediated signaling (RAGE), kinase activity (p38, JNK), and caspase activation (caspase-8, caspase-3).

Main Results:

  • CML-collagen significantly increased calvarial periosteal cell apoptosis in vivo (5-fold) and osteoblastic cell apoptosis in vitro.
  • The apoptotic effect was largely mediated through the Receptor for Advanced Glycation End Products (RAGE).
  • CML-collagen activated p38 and JNK kinases, and inhibition of these pathways significantly reduced apoptosis. The pathway involved caspase-8 and caspase-3 activation, independent of NF-kappaB.
  • Long-term, low-dose exposure and exposure to more differentiated cells enhanced apoptosis.

Conclusions:

  • Advanced glycation end products (AGEs) directly promote osteoblastic cell apoptosis.
  • The RAGE receptor and p38/JNK signaling pathways are critical mediators of AGEs-induced osteoblastic apoptosis.
  • AGEs-induced osteoblastic apoptosis may contribute to impaired bone formation in conditions like diabetes and aging.

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