Aluminum Chloride Induces Osteoblasts Apoptosis via Disrupting Calcium Homeostasis and Activating Ca(2+)/CaMKII Signal Pathway

Biol Trace Elem Res. 2016 Feb;169(2):247-53. doi: 10.1007/s12011-015-0417-1. Epub 2015 Jul 4.

Abstract

Aluminum promotes osteoblast (OB) apoptosis. Apoptosis is induced by the disordered calcium homeostasis. Therefore, to investigate the relationship between Al-induced OB apoptosis and calcium homeostasis, calvarium OBs from neonatal rats (3-4 days) were cultured and exposed to 0.048-mg/mL Al(3+) or 0.048-mg/mL Al(3+) combined with 5 μM BAPTA-AM (OBs were pretreated with 5 μM BAPTA-AM for 1 h, then added 0.048 mg/mL Al(3+)), respectively. Then OB apoptosis rate, intracellular calcium ions concentration ([Ca(2+)]i), mRNA expression level of calmodulin (CaM), and protein expression levels of CaM and p-CaMKII in OBs were examined. The result showed that AlCl3 increased OB apoptosis rate, and [Ca(2+)]i and p-CaMKII expression levels and decreased CaM expression levels, whereas BAPTA-AM relieved the effects. These results proved that AlCl3 induced OB apoptosis by disrupting the intracellular Ca(2+) homeostasis and activating the Ca(2+)/CaMKII signal pathway. Our findings can provide new insights for revealing the apoptosis mechanism of OBs exposed to AlCl3.

Keywords: AlCl3; BAPTA-AM; Ca2+/CaMKII signal pathway; Calcium homeostasis; Osteoblast apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aluminum Chloride
  • Aluminum Compounds / toxicity*
  • Animals
  • Animals, Newborn
  • Apoptosis / drug effects*
  • Calcium / metabolism*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
  • Cells, Cultured
  • Chlorides / toxicity*
  • Homeostasis / drug effects*
  • Osteoblasts / drug effects*
  • Osteoblasts / enzymology
  • Rats
  • Signal Transduction

Substances

  • Aluminum Compounds
  • Chlorides
  • Aluminum Chloride
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium