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Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis

Secreted factors are a key component of stem cell niche and their dysregulation compromises stem cell function. Legumain is a secreted cysteine protease involved in diverse biological processes. Here, we demonstrate that legumain regulates lineage commitment of human bone marrow stromal cells and th...

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Autores principales: Jafari, Abbas, Qanie, Diyako, Andersen, Thomas L., Zhang, Yuxi, Chen, Li, Postert, Benno, Parsons, Stuart, Ditzel, Nicholas, Khosla, Sundeep, Johansen, Harald Thidemann, Kjærsgaard-Andersen, Per, Delaisse, Jean-Marie, Abdallah, Basem M., Hesselson, Daniel, Solberg, Rigmor, Kassem, Moustapha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312427/
https://www.ncbi.nlm.nih.gov/pubmed/28162997
http://dx.doi.org/10.1016/j.stemcr.2017.01.003
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author Jafari, Abbas
Qanie, Diyako
Andersen, Thomas L.
Zhang, Yuxi
Chen, Li
Postert, Benno
Parsons, Stuart
Ditzel, Nicholas
Khosla, Sundeep
Johansen, Harald Thidemann
Kjærsgaard-Andersen, Per
Delaisse, Jean-Marie
Abdallah, Basem M.
Hesselson, Daniel
Solberg, Rigmor
Kassem, Moustapha
author_facet Jafari, Abbas
Qanie, Diyako
Andersen, Thomas L.
Zhang, Yuxi
Chen, Li
Postert, Benno
Parsons, Stuart
Ditzel, Nicholas
Khosla, Sundeep
Johansen, Harald Thidemann
Kjærsgaard-Andersen, Per
Delaisse, Jean-Marie
Abdallah, Basem M.
Hesselson, Daniel
Solberg, Rigmor
Kassem, Moustapha
author_sort Jafari, Abbas
collection PubMed
description Secreted factors are a key component of stem cell niche and their dysregulation compromises stem cell function. Legumain is a secreted cysteine protease involved in diverse biological processes. Here, we demonstrate that legumain regulates lineage commitment of human bone marrow stromal cells and that its expression level and cellular localization are altered in postmenopausal osteoporotic patients. As shown by genetic and pharmacological manipulation, legumain inhibited osteoblast (OB) differentiation and in vivo bone formation through degradation of the bone matrix protein fibronectin. In addition, genetic ablation or pharmacological inhibition of legumain activity led to precocious OB differentiation and increased vertebral mineralization in zebrafish. Finally, we show that localized increased expression of legumain in bone marrow adipocytes was inversely correlated with adjacent trabecular bone mass in a cohort of patients with postmenopausal osteoporosis. Our data suggest that altered proteolytic activity of legumain in the bone microenvironment contributes to decreased bone mass in postmenopausal osteoporosis.
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spelling pubmed-53124272017-02-22 Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis Jafari, Abbas Qanie, Diyako Andersen, Thomas L. Zhang, Yuxi Chen, Li Postert, Benno Parsons, Stuart Ditzel, Nicholas Khosla, Sundeep Johansen, Harald Thidemann Kjærsgaard-Andersen, Per Delaisse, Jean-Marie Abdallah, Basem M. Hesselson, Daniel Solberg, Rigmor Kassem, Moustapha Stem Cell Reports Article Secreted factors are a key component of stem cell niche and their dysregulation compromises stem cell function. Legumain is a secreted cysteine protease involved in diverse biological processes. Here, we demonstrate that legumain regulates lineage commitment of human bone marrow stromal cells and that its expression level and cellular localization are altered in postmenopausal osteoporotic patients. As shown by genetic and pharmacological manipulation, legumain inhibited osteoblast (OB) differentiation and in vivo bone formation through degradation of the bone matrix protein fibronectin. In addition, genetic ablation or pharmacological inhibition of legumain activity led to precocious OB differentiation and increased vertebral mineralization in zebrafish. Finally, we show that localized increased expression of legumain in bone marrow adipocytes was inversely correlated with adjacent trabecular bone mass in a cohort of patients with postmenopausal osteoporosis. Our data suggest that altered proteolytic activity of legumain in the bone microenvironment contributes to decreased bone mass in postmenopausal osteoporosis. Elsevier 2017-02-02 /pmc/articles/PMC5312427/ /pubmed/28162997 http://dx.doi.org/10.1016/j.stemcr.2017.01.003 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Jafari, Abbas
Qanie, Diyako
Andersen, Thomas L.
Zhang, Yuxi
Chen, Li
Postert, Benno
Parsons, Stuart
Ditzel, Nicholas
Khosla, Sundeep
Johansen, Harald Thidemann
Kjærsgaard-Andersen, Per
Delaisse, Jean-Marie
Abdallah, Basem M.
Hesselson, Daniel
Solberg, Rigmor
Kassem, Moustapha
Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis
title Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis
title_full Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis
title_fullStr Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis
title_full_unstemmed Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis
title_short Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis
title_sort legumain regulates differentiation fate of human bone marrow stromal cells and is altered in postmenopausal osteoporosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312427/
https://www.ncbi.nlm.nih.gov/pubmed/28162997
http://dx.doi.org/10.1016/j.stemcr.2017.01.003
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