Monocytic expression of osteoclast-associated receptor (OSCAR) is induced in atherosclerotic mice and regulated by oxidized low-density lipoprotein in vitro

Abstract

The osteoclast-associated receptor (OSCAR), primarily described as a co-stimulatory regulator of osteoclast differentiation, represents a potential link between bone metabolism and vascular biology. Previously, we identified OSCAR as an endothelial cell-derived target of the proatherogenic factor oxidized low density lipoprotein (oxLDL). Since monocytes play an important role in the progression of atherosclerosis, we assessed whether atherogenic stimuli also regulate the expression of OSCAR on monocytes. Four-week-old male wild-type (WT), apolipoprotein e knockout (apoe KO), and LDL receptor knockout (ldlr KO) mice were fed a high-fat diet or normal chow for 6weeks. Peripheral blood mononuclear cells (PBMCs) isolated from the spleen were stained with antibodies against CD14 and OSCAR for subsequent flow cytometric analysis. OSCAR surface expression on CD14-positive monocytes increased 2-fold in PBMCs from apoe KO mice compared to WT mice. Feeding a high-fat diet further increased OSCAR surface expression 1.5-fold in apoe KO mice compared to normal diet. Moreover, OSCAR-positive macrophages were detected in atherosclerotic plaques of apoe KO mice. Interestingly, monocytic OSCAR expression was not altered in ldlr KO mice. In the murine macrophage cell line RAW 264.7, TNFα and oxLDL induced OSCAR mRNA expression by 2-fold and 5-fold (p<0.01), respectively. Blocking the oxLDL receptor LOX-1 and inhibiting the NF-κB pathway prevented OSCAR induction. In conclusion, OSCAR expression in monocytic cells is regulated by proatherogenic stimuli further pointing towards a role in vascular inflammation or plaque vulnerability during atherosclerosis.