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Impact of the Uremic Milieu on the Osteogenic Potential of Mesenchymal Stem Cells
Human mesenchymal stem cells (hMSCs), the precursors of osteoblasts during osteogenesis, play a role in the balance of bone formation and resorption, but their functioning in uremia has not been well defined. To study the effects of the uremic milieu on osteogenic properties, we applied an in vitro...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312090/ https://www.ncbi.nlm.nih.gov/pubmed/25635832 http://dx.doi.org/10.1371/journal.pone.0116468 |
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author | Lanza, Diana Perna, Alessandra F. Oliva, Adriana Vanholder, Raymond Pletinck, Anneleen Guastafierro, Salvatore Di Nunzio, Annarita Vigorito, Carmela Capasso, Giovambattista Jankowski, Vera Jankowski, Joachim Ingrosso, Diego |
author_facet | Lanza, Diana Perna, Alessandra F. Oliva, Adriana Vanholder, Raymond Pletinck, Anneleen Guastafierro, Salvatore Di Nunzio, Annarita Vigorito, Carmela Capasso, Giovambattista Jankowski, Vera Jankowski, Joachim Ingrosso, Diego |
author_sort | Lanza, Diana |
collection | PubMed |
description | Human mesenchymal stem cells (hMSCs), the precursors of osteoblasts during osteogenesis, play a role in the balance of bone formation and resorption, but their functioning in uremia has not been well defined. To study the effects of the uremic milieu on osteogenic properties, we applied an in vitro assay culturing hMSCs in osteogenic medium supplemented with serum from healthy donors and from uremic patients on hemodialysis. Compared to control, serum from uremic patients induces, in hMSC cultures, a modification of several key regulators of bone remodeling, in particular a reduction of the ratio Receptor Activator of Nuclear factor Kappa B Receptor (RANKL) over osteoprotegerin, indicating an adaptive response of the system to favor osteogenesis over osteoclastosis. However, the levels of osteopontin, osteocalcin, and collagen type I, are increased in cell medium, while BMP-2, and alizarin red staining were decreased, pointing to a reduction of bone formation favoring resorption. Selected uremic toxins, such as p-cresylsulfate, p-cresylglucuronide, parathyroid hormone, indoxyl sulfate, asymmetric dimethylarginine, homocysteine, were able to mimic some of the effects of whole serum from uremic patients. Serum from cinacalcet-treated patients antagonizes these effects. Hydrogen sulfide (H2S) donors as well as hemodialysis treatment are able to induce beneficial effects. In conclusion, bone modifications in uremia are influenced by the capability of the uremic milieu to alter hMSC osteogenic differentiation. Cinacalcet, H2S donors and a hemodialysis session can ameliorate the hampered calcium deposition. |
format | Online Article Text |
id | pubmed-4312090 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43120902015-02-13 Impact of the Uremic Milieu on the Osteogenic Potential of Mesenchymal Stem Cells Lanza, Diana Perna, Alessandra F. Oliva, Adriana Vanholder, Raymond Pletinck, Anneleen Guastafierro, Salvatore Di Nunzio, Annarita Vigorito, Carmela Capasso, Giovambattista Jankowski, Vera Jankowski, Joachim Ingrosso, Diego PLoS One Research Article Human mesenchymal stem cells (hMSCs), the precursors of osteoblasts during osteogenesis, play a role in the balance of bone formation and resorption, but their functioning in uremia has not been well defined. To study the effects of the uremic milieu on osteogenic properties, we applied an in vitro assay culturing hMSCs in osteogenic medium supplemented with serum from healthy donors and from uremic patients on hemodialysis. Compared to control, serum from uremic patients induces, in hMSC cultures, a modification of several key regulators of bone remodeling, in particular a reduction of the ratio Receptor Activator of Nuclear factor Kappa B Receptor (RANKL) over osteoprotegerin, indicating an adaptive response of the system to favor osteogenesis over osteoclastosis. However, the levels of osteopontin, osteocalcin, and collagen type I, are increased in cell medium, while BMP-2, and alizarin red staining were decreased, pointing to a reduction of bone formation favoring resorption. Selected uremic toxins, such as p-cresylsulfate, p-cresylglucuronide, parathyroid hormone, indoxyl sulfate, asymmetric dimethylarginine, homocysteine, were able to mimic some of the effects of whole serum from uremic patients. Serum from cinacalcet-treated patients antagonizes these effects. Hydrogen sulfide (H2S) donors as well as hemodialysis treatment are able to induce beneficial effects. In conclusion, bone modifications in uremia are influenced by the capability of the uremic milieu to alter hMSC osteogenic differentiation. Cinacalcet, H2S donors and a hemodialysis session can ameliorate the hampered calcium deposition. Public Library of Science 2015-01-30 /pmc/articles/PMC4312090/ /pubmed/25635832 http://dx.doi.org/10.1371/journal.pone.0116468 Text en © 2015 Lanza et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Lanza, Diana Perna, Alessandra F. Oliva, Adriana Vanholder, Raymond Pletinck, Anneleen Guastafierro, Salvatore Di Nunzio, Annarita Vigorito, Carmela Capasso, Giovambattista Jankowski, Vera Jankowski, Joachim Ingrosso, Diego Impact of the Uremic Milieu on the Osteogenic Potential of Mesenchymal Stem Cells |
title | Impact of the Uremic Milieu on the Osteogenic Potential of Mesenchymal Stem Cells |
title_full | Impact of the Uremic Milieu on the Osteogenic Potential of Mesenchymal Stem Cells |
title_fullStr | Impact of the Uremic Milieu on the Osteogenic Potential of Mesenchymal Stem Cells |
title_full_unstemmed | Impact of the Uremic Milieu on the Osteogenic Potential of Mesenchymal Stem Cells |
title_short | Impact of the Uremic Milieu on the Osteogenic Potential of Mesenchymal Stem Cells |
title_sort | impact of the uremic milieu on the osteogenic potential of mesenchymal stem cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312090/ https://www.ncbi.nlm.nih.gov/pubmed/25635832 http://dx.doi.org/10.1371/journal.pone.0116468 |
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