RT Journal Article
T1 Recombinant IGF-1 Induces Sex-Specific Changes in Bone Composition and Remodeling in Adult Mice with Pappa2 Deficiency
A1 Rubio-Lamia, Leticia Olga
A1 Vargas, Antonio
A1 River, Patricia
A1 López-Gambero, Antonio J.
A1 Tobar, Rubén
A1 Christians, Julian K.
A1 Martín-de-las-Heras, Stella
A1 Rodriguez-de-Fonseca, Fernando
A1 Chowen, Julie A.
A1 Argente, Jesús
A1 Suárez-Pérez, Juan
K1 Proteínas sanguíneas
K1 Embarazo - Complicaciones y secuelas
AB 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.
PB MDPI
YR 2021
FD 2021
LK https://hdl.handle.net/10630/28678
UL https://hdl.handle.net/10630/28678
LA eng
NO 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
NO This research was funded by Instituto de Salud Carlos III (ISCIII), Ministerio de Economía y Competitividad (MINECO) and European Regional Development Funds-European Union (ERDF-EU), grant number PI16/01374 and PI19/00343 (J.S.), PI16/00485 and PI19/00166 (J.A.), and BFU2017–82565-C2-1-R (J.A.C.); NSERC (Canada) Discovery Grant, grant number, 2016-04047 (J.K.C.). J.S. (CPII17/00024) and P.R. (CP19/00068) hold “Miguel Servet” research contracts and A.J.L.-G. holds a i-PFIS research contract (IFI18/00042), all of them from the National System of Health, ISCIII, ERDF-EU.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 22 ene 2026