title: Stimulation of in-vitro angiogenesis by low concentrations of risedronate is mitigated by 1,25-dihydroxyvitamin D3 or 24,25-dihydroxyvitamin D3.
abstract: The nitrogen-containing or nitrogenous bisphosphonates (N-BF) are currently the main class of drugs used for the treatment of diseases characterized by an increased bone resorption. Preliminary data suggest that N-BF have also direct or indirect anti-tumoral effects, and recent evidence suggests that part of the anti-tumoral activity of N-BF may be attributed to their anti-angiogenic capacity when they are used at high concentrations. On the other hand, an optimal vitamin-D status seems to be necessary to maximize the bone response to N-BF. Our aim has been to evaluate the effect of risedronate, alone or in combination with either 1,25(OH)2D3 or 24,25(OH)2D3 (two main vitamin-D metabolites) on parameters related to the angiogenic capacity of human umbilical-vein endothelial cells (HUVEC). The studies of tube formation through in-vitro angiogenesis assays with Matrigel, chemotaxis and migration in a scratch assay showed that low concentrations of risedronate (0.01 to 1μM) stimulated angiogenesis and cellular migration in vitro. The presence of 1,25(OH)2D3 in the medium inhibited tubular-structure formation and cellular migration. In addition, the presence of 1,25 or 24,25(OH)2D3 in the culture medium also decreased the pro-angiogenic effects of low-concentrations of risedronate. These data show the differential effects of different concentrations of vitamin-D metabolites and risedronate on angiogenesis, thus stressing the importance of an adequate vitamin D status during medical treatment with risedronate. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía and RETICEF, Avda. Menéndez Pidal s/n, Córdoba 14004, Spain. Electronic address: jmquesada@uco.es.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Quesada-Gómez
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía and RETICEF, Avda. Menéndez Pidal s/n, Córdoba 14004, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Santiago-Mora
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía and RETICEF, Avda. Menéndez Pidal s/n, Córdoba 14004, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Navarro-Valverde
authors.affiliation: Departamento Bioquímica y Biología Molecular, Universidad de Córdoba, Campus Rabanales C6-1-E17, Campus de Excelencia Internacional Agroalimentario (ceiA3), Córdoba 14071, Spain.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Dorado
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía and RETICEF, Avda. Menéndez Pidal s/n, Córdoba 14004, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Casado-Díaz
mesh_terms: D015650:24,25-Dihydroxyvitamin D 3 / Q000494:pharmacology*; D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D002117:Calcitriol / Q000494:pharmacology*; D012968:Etidronic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D000068296:Risedronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D015650:24,25-Dihydroxyvitamin D 3; D002117:Calcitriol; D000068296:Risedronic Acid; D012968:Etidronic Acid
keywords: 1,25(OH)(2)D(3); 24,25(OH)(2)D(3); Angiogenesis; Risedronate