Bone Abstracts

The osteoclast-associated receptor (OSCAR), primarily described as a co-stimulatory regulator of osteoclast differentiation, represents a novel link between bone metabolism and vascular biology. Previously, we identified OSCAR on endothelial cells responding to the proatherogenic factor oxidized low density lipoprotein (oxLDL). Additionally, OSCAR expression was increased in the aorta of atherogenic apoE-knock-out (apoE-KO) mice, where it was further induced by feeding a high-fat diet. Because monocytes play an important role in the progression of atherosclerosis, we assessed whether atherosclerosis also regulates the expression of OSCAR on monocytes and whether it is regulated by oxLDL or other inflammatory mediators in vitro. Four weeks old male wild-type (WT), apoE-KO and ldlr-(LDL receptor) KO mice were fed a high-fat diet or normal chow for 6 weeks. Thereafter, peripheral blood mononuclear cells (PBMC) were isolated from the spleen by Biocoll density centrifugation to stain the cells with antibodies against CD14 and OSCAR for subsequent flow cytometric analysis. OSCAR surface expression on CD14-positive monocytes was increased twofold in PBMCs from apoE-KO mice compared to WT mice. Feeding a high-fat diet further increased OSCAR surface expression up to 1.5-fold in apoE-KO mice compared to apoE-KO mice fed a normal chow. Similarly, PBMCs from ldlr-KO mice, fed a high-fat diet showed a 1.7-fold increase in OSCAR expression compared to WT receiving the same diet. Additionally, we exposed the murine macrophage cell line RAW 264.7 to oxLDL and TNFα. OSCAR mRNA expression levels were induced by TNFα about threefold whereas oxLDL treated cells showed a sixfold increase after 48 h. Signaling experiments revealed that oxLDL-dependent induction of OSCAR expression can be prevented by blocking the oxLDL receptor LOX-1 and inhibiting the NFκB-pathway. In conclusion, OSCAR expression in RAW 264.7 cells and primary murine CD14-positive cells is regulated by proatherogenic stimuli further confirming its function in the development of atherosclerosis.