Influence of oxidized low-density lipoproteins (LDL) on the viability of osteoblastic cells.
Cardiovascular diseases have recently been noted as potential risk factors for osteoporosis development. Although it is poorly understood how these two pathologies are related, it is a known fact that oxidized low-density lipoproteins (OxLDL) constitute potential determinants for both of them. The current study investigated the metabolism of OxLDL by osteoblasts and its effect on osteoblastic viability. The results obtained show that OxLDL are internalized but not degraded by osteoblasts while they can selectively transfer their CE to these cells. It is also demonstrated that OxLDL induce proliferation at low concentrations but cell death at high concentrations. This reduction of osteoblast viability was associated with lysosomal membrane damage caused by OxLDL as demonstrated by acridine orange relocalization. Accordingly, chloroquine, an inhibitor of lysosomal activity, accentuated cell death induced by OxLDL. Finally, we demonstrate that osteoblasts have the capacity to oxidize LDL and thereby potentially increase the local concentration of OxLDL. Overall, the current study confirms the potential role of OxLDL in the development of osteoporosis given its influence on osteoblastic viability.
Brodeur
Mathieu R
MR
Département des Sciences Biologiques, Université du Québec à Montréal, CP 8888, succ Centre-Ville, Montreal (Quebec), Canada H3C 3P8.
Brissette
Louise
L
Falstrault
Louise
L
Ouellet
Pascale
P
Moreau
Robert
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D008247:Lysosomes / Q000187:drug effects; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010024:Osteoporosis / Q000209:etiology*; D010084:Oxidation-Reduction; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
D008077:Lipoproteins, LDL; D013778:Tetrazolium Salts; D013844:Thiazoles; C099252:oxidized low density lipoprotein; C022616:thiazolyl blue