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


CONCLUSIONS
This highlights the role of OxLDL in bone remodeling and in degenerative disorders other than atherosclerosis, especially in osteoporosis.
Mazière
Cécile
C
INSERM ERI 12 (EA 4292), Amiens, F-80000, France. maziere.cecile@chu-amiens.fr
Savitsky
Valéry
V
Galmiche
Antoine
A
Gomila
Cathy
C
Massy
Ziad
Z
Mazière
Jean-Claude
JC
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002113:Calcification, Physiologic / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015151:Immunoblotting; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053495:Osteopontin / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010710:Phosphates / Q000378:metabolism / Q000494:pharmacology*; D053245:RANK Ligand / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D050659:Core Binding Factor Alpha 1 Subunit; D008077:Lipoproteins, LDL; D010710:Phosphates; D053245:RANK Ligand; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; C099252:oxidized low density lipoprotein; D053495:Osteopontin; D014810:Vitamin E; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium