Publication:
Recombinant IGF-1 Induces Sex-Specific Changes in Bone Composition and Remodeling in Adult Mice with Pappa2 Deficiency

dc.contributor.authorRubio, Leticia
dc.contributor.authorVargas, Antonio
dc.contributor.authorRivera, Patricia
dc.contributor.authorLópez-Gambero, Antonio J.
dc.contributor.authorTovar, Rubén
dc.contributor.authorChristians, Julian K.
dc.contributor.authorMartín-de-las-Heras, Stella
dc.contributor.authorRodríguez de Fonseca, Fernando
dc.contributor.authorChowen, Julie A.
dc.contributor.authorArgente, Jesús
dc.contributor.authorSuárez, Juan
dc.contributor.authoraffiliation[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.
dc.contributor.funderThis 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.
dc.date.accessioned2022-07-19T09:50:44Z
dc.date.available2022-07-19T09:50:44Z
dc.date.issued2021-04-14
dc.description.abstractDeficiency 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.es_ES
dc.description.versionYeses_ES
dc.identifier.citationRubio 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):4048es_ES
dc.identifier.doi10.3390/ijms22084048es_ES
dc.identifier.essn1422-0067
dc.identifier.pmcPMC8070906
dc.identifier.pmid33919940es_ES
dc.identifier.urihttp://hdl.handle.net/10668/3805
dc.journal.titleInternational Journal of Molecular Sciences
dc.language.isoen
dc.page.number18 p.
dc.publisherMDPIes_ES
dc.relation.publisherversionhttps://www.mdpi.com/1422-0067/22/8/4048/htmes_ES
dc.rightsAtribución 4.0 Internacional*
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectApatitees_ES
dc.subjectBonees_ES
dc.subjectCollagenes_ES
dc.subjectGrowthes_ES
dc.subjectIGFBPes_ES
dc.subjectPappalysines_ES
dc.subjectSex differencees_ES
dc.subjectPappa2 deficiencyes_ES
dc.subjectApatitaes_ES
dc.subjectHuesoes_ES
dc.subjectColágenoes_ES
dc.subjectCrecimientoes_ES
dc.subjectProteínas de unión a factor de crecimiento similar a la insulinaes_ES
dc.subjectProteína plasmática asociada al embarazoes_ES
dc.subjectCaracterísticas sexualeses_ES
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Animalses_ES
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Bone Densityes_ES
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Bone Remodelinges_ES
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Bone Remodelinges_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteinses_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Scleroproteins::Extracellular Matrix Proteins::Collagen::Fibrillar Collagens::Collagen Type Ies_ES
dc.subject.meshGene Expression Regulation, Developmentales_ES
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humanses_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins::Insulin-Like Growth Factor Binding Proteins::Insulin-Like Growth Factor Binding Protein 3es_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intercellular Signaling Peptides and Proteins::Somatomedins::Insulin-Like Growth Factor Ies_ES
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Micees_ES
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Genetically Modified::Mice, Transgenic::Mice, Knockoutes_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins::Calcium-Binding Proteins::Osteocalcines_ES
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Musculoskeletal Development::Bone Development::Osteogenesises_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::Cytokines::Osteopontines_ES
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Pregnancy Proteins::Pregnancy-Associated Plasma Protein-Aes_ES
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Sex Characteristicses_ES
dc.titleRecombinant IGF-1 Induces Sex-Specific Changes in Bone Composition and Remodeling in Adult Mice with Pappa2 Deficiencyes_ES
dc.typeresearch article
dc.type.hasVersionVoR
dspace.entity.typePublication

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