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Low extracellular sodium promotes adipogenic commitment of human mesenchymal stromal cells: a novel mechanism for chronic hyponatremia-induced bone loss

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Abstract

Hyponatremia represents an independent risk factor for osteoporosis and fractures, affecting both bone density and quality. A direct stimulation of bone resorption in the presence of reduced extracellular sodium concentrations ([Na+]) has been shown, but the effects of low [Na+] on osteoblasts have not been elucidated. We investigated the effects of a chronic reduction of extracellular [Na+], independently of osmotic stress, on human mesenchymal stromal cells (hMSC) from bone marrow, the common progenitor for osteoblasts and adipocytes. hMSC adhesion and viability were significantly inhibited by reduced [Na+], but their surface antigen profile and immuno-modulatory properties were not altered. In low [Na+], hMSC were able to commit toward both the osteogenic and the adipogenic phenotypes, as demonstrated by differentiation markers analysis. However, the dose-dependent increase in the number of adipocytes as a function of reduced [Na+] suggested a preferential commitment toward the adipogenic phenotype at the expense of osteogenesis. The amplified inhibitory effect on the expression of osteoblastic markers exerted by adipocytes-derived conditioned media in low [Na+] further supported this observation. The analysis of cytoskeleton showed that low [Na+] were associated with disruption of tubulin organization in hMSC-derived osteoblasts, thus suggesting a negative effect on bone quality. Finally, hMSC-derived osteoblasts increased their expression of factors stimulating osteoclast recruitment and activity. These findings confirm that hyponatremia should be carefully taken into account because of its negative effects on bone, in addition to the known neurological effects, and indicate for the first time that impaired osteogenesis may be involved.

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Acknowledgments

The authors wish to thank Ente Cassa di Risparmio di Firenze for supporting the study.

Conflict of interest

Benedetta Fibbi, Susanna Benvenuti, Corinna Giuliani, Cristiana Deledda, Paola Luciani, Monica Monici, Benedetta Mazzanti, Clara Ballerini, and Alessandro Peri declare that they have no conflict of interest.

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Authors and Affiliations

  1. Endocrine Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy

    B. Fibbi, S. Benvenuti, C. Giuliani, C. Deledda, P. Luciani & A. Peri

  2. ASAcampus Joint Laboratory, ASA Research Division, “Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies” (DENOThe), Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence, Italy

    M. Monici

  3. Haematology Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

    B. Mazzanti

  4. Department of NEUROFARBA, University of Florence, Florence, Italy

    C. Ballerini

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Correspondence to A. Peri.

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Fibbi, B., Benvenuti, S., Giuliani, C. et al. Low extracellular sodium promotes adipogenic commitment of human mesenchymal stromal cells: a novel mechanism for chronic hyponatremia-induced bone loss. Endocrine 52, 73–85 (2016). https://doi.org/10.1007/s12020-015-0663-1

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