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Pin1 Null Mice Exhibit Low Bone Mass and Attenuation of BMP Signaling
Bone is constantly formed and resorbed throughout life by coordinated actions of osteoblasts and osteoclasts. However, the molecular mechanisms involved in osteoblast function remain incompletely understood. Here we show, for the first time, that the peptidyl-prolyl isomerase PIN1 controls the osteo...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651169/ https://www.ncbi.nlm.nih.gov/pubmed/23675491 http://dx.doi.org/10.1371/journal.pone.0063565 |
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author | Shen, Zhong-Jian Hu, Jie Ali, Aktar Pastor, Johanne Shiizaki, Kazuhiro Blank, Robert D. Kuro-o, Makoto Malter, James S. |
author_facet | Shen, Zhong-Jian Hu, Jie Ali, Aktar Pastor, Johanne Shiizaki, Kazuhiro Blank, Robert D. Kuro-o, Makoto Malter, James S. |
author_sort | Shen, Zhong-Jian |
collection | PubMed |
description | Bone is constantly formed and resorbed throughout life by coordinated actions of osteoblasts and osteoclasts. However, the molecular mechanisms involved in osteoblast function remain incompletely understood. Here we show, for the first time, that the peptidyl-prolyl isomerase PIN1 controls the osteogenic activity of osteoblasts. Pin1 null mice exhibited an age-dependent decrease in bone mineral density and trabecular bone formation without alteration in cortical bone. Further analysis identified a defect in BMP signaling in Pin1 null osteoblasts but normal osteoclast function. PIN1 interacted with SMAD5 and was required for the expression by primary osteoblasts of osteoblast specific transcription factors (CBFA1 and OSX), ECM (collagen I and OCN) and the formation of bone nodules. Our results thus uncover a novel aspect of the molecular underpinning of osteoblast function and identify a new therapeutic target for bone diseases. |
format | Online Article Text |
id | pubmed-3651169 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-36511692013-05-14 Pin1 Null Mice Exhibit Low Bone Mass and Attenuation of BMP Signaling Shen, Zhong-Jian Hu, Jie Ali, Aktar Pastor, Johanne Shiizaki, Kazuhiro Blank, Robert D. Kuro-o, Makoto Malter, James S. PLoS One Research Article Bone is constantly formed and resorbed throughout life by coordinated actions of osteoblasts and osteoclasts. However, the molecular mechanisms involved in osteoblast function remain incompletely understood. Here we show, for the first time, that the peptidyl-prolyl isomerase PIN1 controls the osteogenic activity of osteoblasts. Pin1 null mice exhibited an age-dependent decrease in bone mineral density and trabecular bone formation without alteration in cortical bone. Further analysis identified a defect in BMP signaling in Pin1 null osteoblasts but normal osteoclast function. PIN1 interacted with SMAD5 and was required for the expression by primary osteoblasts of osteoblast specific transcription factors (CBFA1 and OSX), ECM (collagen I and OCN) and the formation of bone nodules. Our results thus uncover a novel aspect of the molecular underpinning of osteoblast function and identify a new therapeutic target for bone diseases. Public Library of Science 2013-05-10 /pmc/articles/PMC3651169/ /pubmed/23675491 http://dx.doi.org/10.1371/journal.pone.0063565 Text en © 2013 Shen 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 Shen, Zhong-Jian Hu, Jie Ali, Aktar Pastor, Johanne Shiizaki, Kazuhiro Blank, Robert D. Kuro-o, Makoto Malter, James S. Pin1 Null Mice Exhibit Low Bone Mass and Attenuation of BMP Signaling |
title | Pin1 Null Mice Exhibit Low Bone Mass and Attenuation of BMP Signaling |
title_full | Pin1 Null Mice Exhibit Low Bone Mass and Attenuation of BMP Signaling |
title_fullStr | Pin1 Null Mice Exhibit Low Bone Mass and Attenuation of BMP Signaling |
title_full_unstemmed | Pin1 Null Mice Exhibit Low Bone Mass and Attenuation of BMP Signaling |
title_short | Pin1 Null Mice Exhibit Low Bone Mass and Attenuation of BMP Signaling |
title_sort | pin1 null mice exhibit low bone mass and attenuation of bmp signaling |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651169/ https://www.ncbi.nlm.nih.gov/pubmed/23675491 http://dx.doi.org/10.1371/journal.pone.0063565 |
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