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

CEPEDA, SABRINA; SANDOVAL, MARISA; RAUSCHEMBERGER, MARÍA BELÉN; CUTINI, PABLO; CAMPELO, ADRIÁN; MASSHEIMER, VIRGINIA

Buenos Aires

Congreso; XXXII Annual Meeting of the Argentine Association of Osteology and Mineral Metabolism.; 2015

Asociación Argentina de Osteología y Metabolismo Mineral

The close relationship between osteoporosis and cardiovascular disease is knownas 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 (5μM) 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 pb0.02). ALN treatment enhanced nitric oxide (NO) production, either under physiological or supraphysiological extracellular calcium levels (45, 40% above Cont, 1 mM; 5 mM Ca,pb0.02). Similar results were obtained with Gen treatment. The proinflammatory agent lipopolysaccharide (LPS 1μg/mL) was employed as inductor of monocyte adhesion (mφA) to the endothelium (21 ± 3.1 vs 34 ± 1.7 cells/field, Cont vs LPS, pb0.01). When ALN or Gen was added prior to LPS treatment, both agents partially prevented mφA induced by LPS (pb0.01). VSMC transdifferentiation to OB was performed by 25 days incubation with glycerophosphate + Ca. Under these condi-tions, 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 pb0.001). Gen treatment impaired VSMC-OB transdifferentiation (35% reduction in ALP and 25% increase in Ca levels pb0.05), while ALN had no effect. Changes on Ca content were also determined by Alizarin staining. The results suggest a positive effect of ALNandGenonbone andvascular 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.