title: Prevention of Bone Loss in a Model of Postmenopausal Osteoporosis through Adrenomedullin Inhibition.
abstract: Despite recent advances in the understanding and treatment options for osteoporosis, this condition remains a serious public health issue. Adrenomedullin (AM) is a regulatory peptide with reported activity on bone remodeling. To better understand this relationship we built an inducible knockout for AM. An outstanding feature of knockout mice is their heavier weight due, in part, to the presence of denser bones. The femur of knockout animals was denser, had more trabeculae, and a thicker growth plate than wild type littermates. The endocrine influence of AM on bone seems to be elicited through an indirect mechanism involving, at least, the regulation of insulin, glucose, ghrelin, and calcitonin gene-related peptide (CGRP). To confirm the data we performed a pharmacological approach using the AM inhibitor 16311 in a mouse model of osteoporosis. Ovariectomized females showed significant bone mass loss, whereas ovariectomized females treated with 16311 had similar bone density to sham operated females. In conclusion, we propose the use of AM inhibitors for the treatment of osteoporosis and other conditions leading to the loss of bone mass.
authors.affiliation: Angiogenesis Interest Group, Oncology Area, Center for Biomedical Research of La Rioja, Fundación Rioja Salud Logroño, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Martínez-Herrero
authors.affiliation: Angiogenesis Interest Group, Oncology Area, Center for Biomedical Research of La Rioja, Fundación Rioja Salud Logroño, Spain.
authors.forename: Ignacio M
authors.initials: IM
authors.lastname: Larrayoz
authors.affiliation: Angiogenesis Interest Group, Oncology Area, Center for Biomedical Research of La Rioja, Fundación Rioja Salud Logroño, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Ochoa-Callejero
authors.affiliation: Centro de Investigación Biomédica en Red, Aragon Institute of Health SciencesZaragoza, Spain; Group of Structural Mechanics and Materials Modelling, Aragón Institute of Engineering Research (I3A), University of ZaragozaZaragoza, Spain.
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Fernández
authors.affiliation: Centro de Investigación Biomédica en Red, Aragon Institute of Health SciencesZaragoza, Spain; Group of Structural Mechanics and Materials Modelling, Aragón Institute of Engineering Research (I3A), University of ZaragozaZaragoza, Spain.
authors.forename: Alexis
authors.initials: A
authors.lastname: Allueva
authors.affiliation: Centro de Investigación Biomédica en Red, Aragon Institute of Health SciencesZaragoza, Spain; Group of Structural Mechanics and Materials Modelling, Aragón Institute of Engineering Research (I3A), University of ZaragozaZaragoza, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Ochoa
authors.affiliation: Angiogenesis Interest Group, Oncology Area, Center for Biomedical Research of La Rioja, Fundación Rioja Salud Logroño, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Martínez
keywords: adrenomedullin; bone physiology; inducible knockout; osteoporosis; ovariectomized mice; small molecule inhibitor