Characterization of oxidized low-density lipoprotein-induced hormesis-like effects in osteoblastic cells

Am J Physiol Cell Physiol. 2008 Apr;294(4):C1021-33. doi: 10.1152/ajpcell.00361.2007. Epub 2008 Feb 20.


Epidemiological studies indicate that patients suffering from atherosclerosis are predisposed to develop osteoporosis. Atherogenic determinants such as oxidized low-density lipoprotein (oxLDL) particles have been shown both to stimulate the proliferation and promote apoptosis of bone-forming osteoblasts. Given such opposite responses, we characterized the oxLDL-induced hormesis-like effects in osteoblasts. Biphasic 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reductive activity responses were induced by oxLDL where low concentrations (10-50 microg/ml) increased and high concentrations (from 150 microg/ml) reduced the MTT activity. Cell proliferation stimulation by oxLDL partially accounted for the increased MTT activity. No alteration of mitochondria mass was noticed, whereas low concentrations of oxLDL induced mitochondria hyperpolarization and increased the cellular levels of reactive oxygen species (ROS). The oxLDL-induced MTT activity was not related to intracellular ROS levels. OxLDL increased NAD(P)H-associated cellular fluorescence and flavoenzyme inhibitor diphenyleneiodonium reduced basal and oxLDL-induced MTT activity, suggesting an enhancement of NAD(P)H-dependent cellular reduction potential. Low concentrations of oxLDL reduced cellular thiol content and increased metallothionein expression, suggesting the induction of compensatory mechanisms for the maintenance of cell redox state. These concentrations of oxLDL reduced osteoblast alkaline phosphatase activity and cell migration. Our results indicate that oxLDL particles cause hormesis-like response with the stimulation of both proliferation and cellular NAD(P)H-dependent reduction potential by low concentrations, whereas high concentrations lead to reduction of MTT activity associated with the cell death. Given the effects of low concentrations of oxLDL on osteoblast functions, oxLDL may contribute to the impairment of bone remodeling equilibrium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Atherosclerosis / complications
  • Cell Line
  • Cell Proliferation / drug effects
  • Chloroquine / pharmacology
  • Humans
  • Lipoproteins, LDL / administration & dosage
  • Lipoproteins, LDL / pharmacology*
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Osteoblasts / cytology
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • Osteoporosis / etiology
  • Reactive Oxygen Species / metabolism
  • Tetrazolium Salts
  • Thiazoles


  • Lipoproteins, LDL
  • Reactive Oxygen Species
  • Tetrazolium Salts
  • Thiazoles
  • oxidized low density lipoprotein
  • Chloroquine
  • thiazolyl blue