Oxidized low density lipoprotein inhibits phosphate signaling and phosphate-induced mineralization in osteoblasts. Involvement of oxidative stress

Biochim Biophys Acta. 2010 Nov;1802(11):1013-9. doi: 10.1016/j.bbadis.2010.07.010. Epub 2010 Jul 25.


Background: It is well admitted that oxidized LDL (OxLDL) plays a major role in the generation and progression of atherosclerosis. Since atherosclerosis is often accompanied by osteoporosis, the effects of OxLDL on phosphate-induced osteoblast mineralization were investigated.

Methods: Calcium deposition, expression of osteoblast markers and inorganic phosphate (Pi) signaling were determined under OxLDL treatment.

Results: OxLDL, within the range of 10-50 μg protein/ml, inhibited Pi-induced UMR106 rat osteoblast mineralization. In parallel, the expression of Cbfa1/Runx2 transcription factor was decreased, and the intracellular level of the osteoblast marker osteopontin (OPN) was reduced. The extracellular level of another marker, receptor activator of nuclear factor kappa B ligand (RANKL), was also diminished. OxLDL inhibited Pi signaling via ERK/JNK kinases and AP1/CREB transcription factors. OxLDL triggered the generation of reactive oxygen species (ROS), either in the absence or presence of Pi. Furthermore, the effects of OxLDL on Pi-induced mineralization, generation of ROS and extracellular level OPN were reproduced by the lipid extract of the particle, whereas the antioxidant vitamin E prevented them.

Conclusions: This work demonstrates that OxLDL, by generation of an oxidative stress, inhibits of Pi signaling and impairs Pi-induced osteoblast differentiation.

General significance: This highlights the role of OxLDL in bone remodeling and in degenerative disorders other than atherosclerosis, especially in osteoporosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Calcification, Physiologic / drug effects
  • Calcium / metabolism*
  • Cell Line, Tumor
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Dose-Response Relationship, Drug
  • Immunoblotting
  • Lipoproteins, LDL / pharmacology*
  • Mitogen-Activated Protein Kinases / metabolism
  • Osteoblasts / cytology
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • Osteopontin / metabolism
  • Oxidative Stress / drug effects
  • Phosphates / metabolism
  • Phosphates / pharmacology*
  • RANK Ligand / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Transcription Factor AP-1 / metabolism
  • Vitamin E / pharmacology


  • Antioxidants
  • Core Binding Factor Alpha 1 Subunit
  • Lipoproteins, LDL
  • Phosphates
  • RANK Ligand
  • Reactive Oxygen Species
  • Transcription Factor AP-1
  • oxidized low density lipoprotein
  • Osteopontin
  • Vitamin E
  • Mitogen-Activated Protein Kinases
  • Calcium