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Impact of the uremic milieu on the osteogenic potential of mesenchymal stem cells

(2015) PLOS ONE. 10(1).
Author
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Abstract
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.
Keywords
HYDROGEN-SULFIDE, MINERAL METABOLISM, HEMODIALYSIS-PATIENTS, ALIZARIN RED-S, SECONDARY HYPERPARATHYROIDISM, BONE TURNOVER, RENAL-FAILURE, IN-VIVO, MARKERS, EXPRESSION

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Citation

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MLA
Lanza, Diana et al. “Impact of the Uremic Milieu on the Osteogenic Potential of Mesenchymal Stem Cells.” PLOS ONE 10.1 (2015): n. pag. Print.
APA
Lanza, D., Perna, A. F., Oliva, A., Vanholder, R., Pletinck, A., Guastafierro, S., Di Nunzio, A., et al. (2015). Impact of the uremic milieu on the osteogenic potential of mesenchymal stem cells. PLOS ONE, 10(1).
Chicago author-date
Lanza, Diana, Alessandra F Perna, Adriana Oliva, Raymond Vanholder, Anneleen Pletinck, Salvatore Guastafierro, Annarita Di Nunzio, et al. 2015. “Impact of the Uremic Milieu on the Osteogenic Potential of Mesenchymal Stem Cells.” Plos One 10 (1).
Chicago author-date (all authors)
Lanza, Diana, Alessandra F Perna, Adriana Oliva, Raymond Vanholder, Anneleen Pletinck, Salvatore Guastafierro, Annarita Di Nunzio, Carmela Vigorito, Giovambattista Capasso, Vera Jankowski, Joachim Jankowski, and Diego Ingrosso. 2015. “Impact of the Uremic Milieu on the Osteogenic Potential of Mesenchymal Stem Cells.” Plos One 10 (1).
Vancouver
1.
Lanza D, Perna AF, Oliva A, Vanholder R, Pletinck A, Guastafierro S, et al. Impact of the uremic milieu on the osteogenic potential of mesenchymal stem cells. PLOS ONE. 2015;10(1).
IEEE
[1]
D. Lanza et al., “Impact of the uremic milieu on the osteogenic potential of mesenchymal stem cells,” PLOS ONE, vol. 10, no. 1, 2015.
@article{6868965,
  abstract     = {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.},
  articleno    = {e0116468},
  author       = {Lanza, Diana and Perna, Alessandra F and Oliva, Adriana and Vanholder, Raymond and Pletinck, Anneleen and Guastafierro, Salvatore and Di Nunzio, Annarita and Vigorito, Carmela and Capasso, Giovambattista and Jankowski, Vera and Jankowski, Joachim and Ingrosso, Diego},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keywords     = {HYDROGEN-SULFIDE,MINERAL METABOLISM,HEMODIALYSIS-PATIENTS,ALIZARIN RED-S,SECONDARY HYPERPARATHYROIDISM,BONE TURNOVER,RENAL-FAILURE,IN-VIVO,MARKERS,EXPRESSION},
  language     = {eng},
  number       = {1},
  pages        = {17},
  title        = {Impact of the uremic milieu on the osteogenic potential of mesenchymal stem cells},
  url          = {http://dx.doi.org/10.1371/journal.pone.0116468},
  volume       = {10},
  year         = {2015},
}

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