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Characterization of skeletal alterations in a model of prematurely aging mice

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Abstract

An age-related bone loss occurs, apparently associated with the concomitant increase in an oxidative stress situation. However, the underlying mechanisms of age-related osteopenia are ill defined since these studies are time consuming and require the use of many animals (mainly rodents). Here, we aimed to characterize for the first time the bone status of prematurely aging mice (PAM), which exhibit an increased oxidative stress. Tibiae from adult (6 months) PAM show an increase in bone mineral density (BMD) and bone mineral content (assessed by bone densitometry) versus those in their normal counterparts (non-prematurely aging mice, NPAM) and similarly decreased in both kinds of mouse with age. However, at this bone site, trabecular BMD (determined by μ-computerized tomography) was similar in both adult PAM and old (18 months) NPAM. Femurs from these groups of mice present an increase in oxidative stress, inflammation, osteoclastogenic, and adipogenic markers, but a decrease in the gene expression of osteoblastic differentiation markers and of the Wnt/β-catenin pathway. Our findings show that adult PAM recapitulate various age-related bone features, and thus are a suitable model for premature bone senescence studies.

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Acknowledgments

We thank Elena Andrés [Molecular Imaging Unit, Centro Nacional de Investigaciones Oncológicas (CNIO)] for her technical assistance with μCT measurements. This study was supported by grants from Instituto de Salud Carlos III (PI080922, PI11/00449, RETICEF-RD06/0013/1002, and RETICEF-RD06/0013/0003), Spanish Ministerio de Ciencia e Innovación (MCINN) (BFU2008-04336), and Fundación de Investigación Médica Mutua Madrileña. S.P-N. and D.L. are recipients of a research contract from RETICEF (RD06/0013/1002) and Comunidad Autónoma de Madrid (S-2009/Mat-1472), respectively. A.A. is an associate researcher from CIBERDEM.

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Authors and Affiliations

  1. Bone and Mineral Metabolism Laboratory, Instituto de Investigación Sanitaria (IIS)-Fundación Jiménez Díaz, Avda. Reyes Católicos, 2, 28040, Madrid, Spain

    Sergio Portal-Núñez, Daniel Lozano & Pedro Esbrit

  2. Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad (RETICEF), Instituto de Salud Carlos III, Madrid, Spain

    Sergio Portal-Núñez, Rashed Manassra, Daniel Lozano, Mónica De la Fuente & Pedro Esbrit

  3. Department of Animal Physiology II, Universidad Complutense de Madrid, Madrid, Spain

    Rashed Manassra & Mónica De la Fuente

  4. Department of Metabolism, Nutrition & Hormones, IIS-Fundación Jiménez Díaz, Madrid, Spain

    Alicia Acitores & María L. Villanueva-Peñacarrillo

  5. Centro de Investigaciones Biomédicas en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain

    Alicia Acitores & María L. Villanueva-Peñacarrillo

  6. Molecular Imaging Unit, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain

    Francisca Mulero

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  1. Sergio Portal-Núñez
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  2. Rashed Manassra
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  3. Daniel Lozano
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  7. Mónica De la Fuente
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  8. Pedro Esbrit
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Correspondence to Sergio Portal-Núñez.

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Portal-Núñez, S., Manassra, R., Lozano, D. et al. Characterization of skeletal alterations in a model of prematurely aging mice. AGE 35, 383–393 (2013). https://doi.org/10.1007/s11357-011-9372-8

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  • DOI: https://doi.org/10.1007/s11357-011-9372-8

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