Alendronate and genistein actions on bone and vascular system: A comparative study

CEPEDA S.; SANDOVAL M.; RAUSCHEMBERGER M.B.; CUTINI P.; CAMPELO A.; MASSHEIMER V.

Sierra de la Ventana

Congreso; XXXII Reunión Anual de la AAOMM; 2015

The close relationship between osteoporosis and cardiovascular disease is known as bone-vascular interaction. Alendronate (ALN) is an antiresorptive drug used in osteoporosis disease treatment and genistein (Gen) is a dietary supplement with potential vascular protective properties. The effect of ALN (5 μM) and Gen (10 nM) on cellular events involved on vascular calcification was studied. The experimental systems employed were: 1-murine osteoblastic cell line (MC3T3); 2-vascular endothelial cell cultures; 3-vascular smooth muscle cells (VSMC) induced to osteoblastic transdifferentiation (VSMC-OB). The effect of Gen or ALN on osteoblasts differentiation was evidenced by an increase on MC3T3 alkaline phosphatase activity (ALP) induced by both agonists (37%; 131%, above Cont, Gen; ALN p < 0.02). ALN treatment enhanced nitric oxide (NO) production, either under physiological or supraphysiological extracellular calcium levels (45, 40% above Cont, 1 mM; 5 mM Ca, p < 0.02). Similar results were obtained with Gen treatment. The proinflammatory agent lipopolysaccharide (LPS 1 μg/mL) was employed as inductor of monocyte adhesion (mφA) to the endothelium (21 ± 3.1 vs 34 ± 1.7 cells/field, Cont vs LPS, p < 0.01). When ALN or Gen was added prior to LPS treatment, both agents partially prevented mφA induced by LPS (p < 0.01). VSMC transdifferentiation to OB was performed by 25 days incubation with glycerophosphate + Ca. Under these conditions, VSMC-OB exhibited a marked increase ALP activity and on extracellular Ca levels compared to native VSMC (ALP 438 ± 35 vs 34 ± 1.8 IU/g prot.; Ca 71 ± 8.8 vs 28 ± 1.9 mg/g prot., VSMC-OB vs native VSMC p < 0.001). Gen treatment impaired VSMC-OB transdifferentiation (35% reduction in ALP and 25% increase in Ca levels p < 0.05), while ALN had no effect. Changes on Ca content were also determined by Alizarin staining. The results suggest a positive effect of ALN and Gen on bone and vascular system, elicited by the stimulation of osteoblasts differentiation or via an impairment of vascular cellular injury events, even though Gen showed a potential greater action.