| Přispěvatelé: |
[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., 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. |
| Popis: |
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. |
