Similar effects of estrone on vascular and bone tissues: ¿Risk or benefit?

Abstract

It is known that the decrease in estrogen levels during menopause negatively affects bone tissue and vascular function. We have previously shown that E1 modulates the cellular events involved in atherogenesis such as vascular smooth muscle cells (VSMC) proliferation and migration, and monocyte/platelet adhesion to endothelium. Vascular calcification represents the advanced stage of atherogenesis, where VSMC transdifferentiation on bone like cells plays a crucial role. The aim of this work was to compare the effect of 10 nM E1 (48 h) on murine calvarial osteoblasts (OB), and on vascular smooth muscular cells transdifferentiated into osteoblasts (VSMC-OB) by incubation in a procalcification medium (10 mM glycerophosphate) for 21 days. We focused our attention on cell differentiation. E1 increased cell proliferation on both cellular types either using MTT assay (39 vs 27% a/each C, OB vs VSMC-OB, p<0.05) or cell counting technique (41 vs 28% a/each C, p<0.05, OB vs VSMC-OB). On OB, E1 treatment stimulated ALP activity (4.64 ± 0.32vs3.37 ± 0.25; E1vsC; x10-2 IU/mg prot., p<0.001), calcium deposition (40,2% a/C,p<0.05; alizarin red staining) and collagen in extracellular matrix visualized by Sirius red staining (↑21% a/C,p<0.05). Similar results were obtained when CMLV-OB cells were employed. E1 enhanced ALP activity (3,72±0,25vs3,00±0,14; E1vsC, x10-2 IU/mg prot,p<0,001) and the number and size of calcification nodules in extracellular matrix (56% a/C,p<0,05). Simultaneously, E1 decreased calcium content in culture medium (735,0±30,5vs468,2±21,1;C vs E1,µg Ca/mg prot.,p<0,001). Indeed E1 enhanced extracellular collagen deposition in CMLV-OB cells (↑19 % a/C,p<0,05). The results presented in this work show a similar action of E1 in both cellular systems. The data suggests an opposite physiological relevance: a beneficial action at bone level favouring osteoblastogenesis and, a deleterious one at vascular homeostasis, promoting vascular calcification.