RT Journal Article
T1 Recombinant IGF-1 Induces Sex-Specific Changes in Bone Composition and Remodeling in Adult Mice with Pappa2 Deficiency
A1 Rubio, Leticia
A1 Vargas, Antonio
A1 Rivera, Patricia
A1 López-Gambero, Antonio J.
A1 Tovar, Rubén
A1 Christians, Julian K.
A1 Martín-de-las-Heras, Stella
A1 Rodríguez de Fonseca, Fernando
A1 Chowen, Julie A.
A1 Argente, Jesús
A1 Suárez, Juan
K1 Apatite
K1 Bone
K1 Collagen
K1 Growth
K1 IGFBP
K1 Pappalysin
K1 Sex difference
K1 Pappa2 deficiency
K1 Apatita
K1 Hueso
K1 Colágeno
K1 Crecimiento
K1 Proteínas de unión a factor de crecimiento similar a la insulina
K1 Proteína plasmática asociada al embarazo
K1 Características sexuales
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 2021-04-14
LK http://hdl.handle.net/10668/3805
UL http://hdl.handle.net/10668/3805
LA en
NO Rubio L, Vargas A, Rivera P, López-Gambero AJ, Tovar R, Christians JK, 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 Apr 14;22(8):4048
DS RISalud
RD Apr 18, 2025