ESPE Abstracts (2019) 92 FC14.3

PAPP-A2 Deficiency Induces Sex-Specific Changes in Hydroxyapatite-(CaOH) Crystallinity and the Effects of IGF-1 on Bone Composition in Adult Mice

Antonio Vargas1, Leticia Rubio2, Patricia Rivera3, Julian Christians4, Fernando Rodríguez de Fonseca1, Julie Chowen3,5,6,7, Juan Suárez1, Jesús Argente3,5,6,7


1Instituto de Investigación Biomédica de Málaga (IBIMA), UGC Salud Mental, Universidad de Málaga, Hospital Universitario Regional de Málaga, Málaga, Spain. 2Department of Anatomy, and Forensic and Legal Medicine, Universidad de Málaga, Málaga, Spain. 3Hospital Infantil Universitario Niño Jesús. Universidad Autónoma de Madrid, Madrid, Spain. 4Simon Fraser University. Department of Biological Sciences, Burnaby, Canada. 5Hospital de la Princesa Research Institute, Madrid, Spain. 6Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y NutriciÓn (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. 7IMDEA Food Institute, CEI UAM + CSIC, Madrid, Spain


Deficiency of pregnancy-associated plasma protein-A2 (PAPP-A2), a regulator of IGF-1 availability, causes postnatal growth failure in humans and mice, at least in part through dysregulation of bone size and density. The present study aimed to determine the effects of Pappa2 gene deletion and the response to recombinant murine IGF-1 (rmIGF-1) on femur microstructure and composition. Hydroxyapatite-related crystallography and ionic substitutions were analyzed by X-ray powder diffraction (XRD) and Attenuated Total Reflection-Fourier Transform Infra-Red (ATR-FTIR) spectroscopy. Gene expression of members of the IGF-1 system was measured in tibia. Male and female Pappa2 knock-out (ko/ko) mice had reduced body length in the peripubertal and adult periods. In adulthood, the femurs and tibias were shorter in Pappa2ko/ko mice of both sexes and weighed relatively less in Pappa2ko/ko males compared to same-sex controls. Pappa2ko/ko male bone had: 1) Altered hydroxyapatite-(CaOH)-related crystallinity and crystallite size; 2) Increased content of phosphates (PO43-) and carbonates (CO32; C-O); 3) Increased expression of Igfbp3, Igfbp5 and Igfals; and 4) Dynamic increases in phosphate (PO43-) and carbonate (C-O) content, and decreases in amide (OH-, C=O) content after a single administration of rmIGF-1 (0.3 mg/kg). Pappa2ko/ko female bone had: 1) No change in crystallinity or ionic content; 2) Reduced expression of Igfbp3 and Igfbp5; and 3) Increased content of phosphates (PO43-), carbonates (CO32; C-O) and amides (OH) and 4) Higher expression of Igfbp3 and Igfbp5 after rmIGF-1 administration. In summary, acute treatment with recombinant IGF-1 modifies hydroxyapatite-related ionic substitutions and local IGF-1 system in the bones of mice with Pappa2 deficiency. These effects depend on sex and provide important insights into IGF-1 efficacy as potential therapy for growth failure.

Article tools

My recent searches

No recent searches.