2026-08-29T12:53:45Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/183102024-11-28T14:52:57Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927col_20.500.12105_16980
Repisalud
author
Rubio, Leticia
author
Vargas, Antonio
author
Rivera, Patricia
author
López-Gambero, Antonio J.
author
Tovar, Rubén
author
Christians, Julian K.
author
Martín-de-las-Heras, Stella
author
Rodríguez de Fonseca, Fernando
author
Chowen, Julie A.
author
Argente, Jesús
author
Suárez, Juan
authoraffiliation
[Rubio,L; Martín-de-las-Heras,S; Suárez,J] Departamento de Anatomía Humana, Medicina Legal e Historia de la Ciencia, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain. [Vargas,A; Rivera,P; López-Gambero,AJ; Tovar,R; Rodríguez de Fonseca,F; Suárez,J] Unidad de Gestión Clínica de Salud Mental, IBIMA, Hospital Regional Universitario de Málaga, Málaga, Spain. [Christians,JK] Department of Biological Sciences, Simon Fraser University, Burnaby, , Canada. [Chowen,JA; Argente,J] Department of Endocrinology, Instituto de Investigación Biomédica la Princesa, Hospital Infantil Universitario Niño Jesús, Madrid, Spain. [Chowen,JA; Argente,J] Centro de Investigación Biomédica en Red Fisiología de la Obesidad y Nutrición (CIBEROBN), Madrid, Spain. [Chowen,JA; Argente,J] IMDEA Food Institute, Campus of International Excellence (CEI) UAM + CSIC, Madrid, Spain. [Argente,J] Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain.
2024-02-19T15:26:51Z
2024-02-19T15:26:51Z
2021-04-14
10.3390/ijms22084048
1422-0067
International Journal of Molecular Sciences
http://hdl.handle.net/10668/3805
33919940
http://hdl.handle.net/20.500.12105/18310
Deficiency of pregnancy-associated plasma protein-A2 (PAPP-A2), an IGF-1 availability regulator, causes postnatal growth failure and dysregulation of bone size and density. The present study aimed to determine the effects of recombinant murine IGF-1 (rmIGF-1) on bone composition and remodeling in constitutive Pappa2 knock-out (ko/ko) mice. To address this challenge, X-ray diffraction (XRD), attenuated total reflection-fourier transform infra-red (ATR-FTIR) spectroscopy and gene expression analysis of members of the IGF-1 system and bone resorption/formation were performed. Pappa2ko/ko mice (both sexes) had reduced body and bone length. Male Pappa2ko/ko mice had specific alterations in bone composition (mineral-to-matrix ratio, carbonate substitution and mineral crystallinity), but not in bone remodeling. In contrast, decreases in collagen maturity and increases in Igfbp3, osteopontin (resorption) and osteocalcin (formation) characterized the bone of Pappa2ko/ko females. A single rmIGF-1 administration (0.3 mg/kg) induced short-term changes in bone composition in Pappa2ko/ko mice (both sexes). rmIGF-1 treatment in Pappa2ko/ko females also increased collagen maturity, and Igfbp3, Igfbp5, Col1a1 and osteopontin expression. In summary, acute IGF-1 treatment modifies bone composition and local IGF-1 response to bone remodeling in mice with Pappa2 deficiency. These effects depend on sex and provide important insights into potential IGF-1 therapy for growth failure and bone loss and repair.
eng
Apatite
Bone
Collagen
Growth
IGFBP
Pappalysin
Sex difference
Pappa2 deficiency
Apatita
Hueso
Colágeno
Crecimiento
Proteínas de unión a factor de crecimiento similar a la insulina
Proteína plasmática asociada al embarazo
Características sexuales
Recombinant IGF-1 Induces Sex-Specific Changes in Bone Composition and Remodeling in Adult Mice with Pappa2 Deficiency
research article