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Lrp5 Is Not Required for the Proliferative Response of Osteoblasts to Strain but Regulates Proliferation and Apoptosis in a Cell Autonomous Manner

Although Lrp5 is known to be an important contributor to the mechanisms regulating bone mass, its precise role remains unclear. The aim of this study was to establish whether mutations in Lrp5 are associated with differences in the growth and/or apoptosis of osteoblast-like cells and their prolifera...

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Autores principales: Javaheri, Behzad, Sunters, Andrew, Zaman, Gul, Suswillo, Rosemary F. L., Saxon, Leanne K., Lanyon, Lance E., Price, Joanna S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342322/
https://www.ncbi.nlm.nih.gov/pubmed/22567110
http://dx.doi.org/10.1371/journal.pone.0035726
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author Javaheri, Behzad
Sunters, Andrew
Zaman, Gul
Suswillo, Rosemary F. L.
Saxon, Leanne K.
Lanyon, Lance E.
Price, Joanna S.
author_facet Javaheri, Behzad
Sunters, Andrew
Zaman, Gul
Suswillo, Rosemary F. L.
Saxon, Leanne K.
Lanyon, Lance E.
Price, Joanna S.
author_sort Javaheri, Behzad
collection PubMed
description Although Lrp5 is known to be an important contributor to the mechanisms regulating bone mass, its precise role remains unclear. The aim of this study was to establish whether mutations in Lrp5 are associated with differences in the growth and/or apoptosis of osteoblast-like cells and their proliferative response to mechanical strain in vitro. Primary osteoblast-like cells were derived from cortical bone of adult mice lacking functional Lrp5 (Lrp5(−/−)), those heterozygous for the human G171V High Bone Mass (HBM) mutation (LRP5 (G171V)) and their WT littermates (WT(Lrp5), WT(HBM)). Osteoblast proliferation over time was significantly higher in cultures of cells from LRP5 (G171V) mice compared to their WT(HBM) littermates, and lower in Lrp5(−/−) cells. Cells from female LRP5 (G171V) mice grew more rapidly than those from males, whereas cells from female Lrp5(−/−) mice grew more slowly than those from males. Apoptosis induced by serum withdrawal was significantly higher in cultures from Lrp5(−/−) mice than in those from WT(HBM) or LRP5 (G171V) mice. Exposure to a single short period of dynamic mechanical strain was associated with a significant increase in cell number but this response was unaffected by genotype which also did not change the ‘threshold’ at which cells responded to strain. In conclusion, the data presented here suggest that Lrp5 loss and gain of function mutations result in cell-autonomous alterations in osteoblast proliferation and apoptosis but do not alter the proliferative response of osteoblasts to mechanical strain in vitro.
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spelling pubmed-33423222012-05-07 Lrp5 Is Not Required for the Proliferative Response of Osteoblasts to Strain but Regulates Proliferation and Apoptosis in a Cell Autonomous Manner Javaheri, Behzad Sunters, Andrew Zaman, Gul Suswillo, Rosemary F. L. Saxon, Leanne K. Lanyon, Lance E. Price, Joanna S. PLoS One Research Article Although Lrp5 is known to be an important contributor to the mechanisms regulating bone mass, its precise role remains unclear. The aim of this study was to establish whether mutations in Lrp5 are associated with differences in the growth and/or apoptosis of osteoblast-like cells and their proliferative response to mechanical strain in vitro. Primary osteoblast-like cells were derived from cortical bone of adult mice lacking functional Lrp5 (Lrp5(−/−)), those heterozygous for the human G171V High Bone Mass (HBM) mutation (LRP5 (G171V)) and their WT littermates (WT(Lrp5), WT(HBM)). Osteoblast proliferation over time was significantly higher in cultures of cells from LRP5 (G171V) mice compared to their WT(HBM) littermates, and lower in Lrp5(−/−) cells. Cells from female LRP5 (G171V) mice grew more rapidly than those from males, whereas cells from female Lrp5(−/−) mice grew more slowly than those from males. Apoptosis induced by serum withdrawal was significantly higher in cultures from Lrp5(−/−) mice than in those from WT(HBM) or LRP5 (G171V) mice. Exposure to a single short period of dynamic mechanical strain was associated with a significant increase in cell number but this response was unaffected by genotype which also did not change the ‘threshold’ at which cells responded to strain. In conclusion, the data presented here suggest that Lrp5 loss and gain of function mutations result in cell-autonomous alterations in osteoblast proliferation and apoptosis but do not alter the proliferative response of osteoblasts to mechanical strain in vitro. Public Library of Science 2012-05-02 /pmc/articles/PMC3342322/ /pubmed/22567110 http://dx.doi.org/10.1371/journal.pone.0035726 Text en Javaheri 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
Javaheri, Behzad
Sunters, Andrew
Zaman, Gul
Suswillo, Rosemary F. L.
Saxon, Leanne K.
Lanyon, Lance E.
Price, Joanna S.
Lrp5 Is Not Required for the Proliferative Response of Osteoblasts to Strain but Regulates Proliferation and Apoptosis in a Cell Autonomous Manner
title Lrp5 Is Not Required for the Proliferative Response of Osteoblasts to Strain but Regulates Proliferation and Apoptosis in a Cell Autonomous Manner
title_full Lrp5 Is Not Required for the Proliferative Response of Osteoblasts to Strain but Regulates Proliferation and Apoptosis in a Cell Autonomous Manner
title_fullStr Lrp5 Is Not Required for the Proliferative Response of Osteoblasts to Strain but Regulates Proliferation and Apoptosis in a Cell Autonomous Manner
title_full_unstemmed Lrp5 Is Not Required for the Proliferative Response of Osteoblasts to Strain but Regulates Proliferation and Apoptosis in a Cell Autonomous Manner
title_short Lrp5 Is Not Required for the Proliferative Response of Osteoblasts to Strain but Regulates Proliferation and Apoptosis in a Cell Autonomous Manner
title_sort lrp5 is not required for the proliferative response of osteoblasts to strain but regulates proliferation and apoptosis in a cell autonomous manner
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342322/
https://www.ncbi.nlm.nih.gov/pubmed/22567110
http://dx.doi.org/10.1371/journal.pone.0035726
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