Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/18310
Título
Recombinant IGF-1 Induces Sex-Specific Changes in Bone Composition and Remodeling in Adult Mice with Pappa2 Deficiency
Autor(es)
Fecha de publicación
2021-04-14
Idioma
Inglés
Tipo de documento
research article
Resumen
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.
Palabras clave
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
MESH
Animals | Bone Density | Bone Remodeling | Bone Remodeling | Carrier Proteins | Collagen Type I | Gene Expression Regulation, Developmental | Humans | Insulin-Like Growth Factor Binding Protein 3 | Insulin-Like Growth Factor I | Mice | Mice, Knockout | Osteocalcin | Osteogenesis | Osteopontin | Pregnancy-Associated Plasma Protein-A | Sex Characteristics
Versión en línea
DOI
Aparece en las colecciones
Acceso a texto completo