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oai:riuma.uma.es:10630/286782026-02-03T11:05:04Zcom_10630_2254col_10630_37953

00925njm 22002777a 4500 dc Rubio-Lamia, Leticia Olga author Vargas, Antonio author River, Patricia author López-Gambero, Antonio J. author Tobar, Rubén author Christians, Julian K. author Martín-de-las-Heras, Stella author Rodriguez-de-Fonseca, Fernando author Chowen, Julie A. author Argente, Jesús author Suárez-Pérez, Juan author 2021 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. Rubio, L.; Vargas, A.; Rivera, P.; López-Gambero, A.J.; Tovar, R.; Christians, J.K.; Martín-de-las-Heras, S.; Rodríguez de Fonseca, F.; Chowen, J.A.; Argente, J.; et al. Recombinant IGF-1 Induces Sex-Specific Changes in Bone Composition and Remodeling in Adult Mice with Pappa2 Deficiency. Int. J. Mol. Sci. 2021, 22, 4048. https://doi.org/10.3390/ijms22084048 https://hdl.handle.net/10630/28678 10.3390/ijms22084048 Proteínas sanguíneas Embarazo - Complicaciones y secuelas Recombinant IGF-1 Induces Sex-Specific Changes in Bone Composition and Remodeling in Adult Mice with Pappa2 Deficiency