Mesenchymal stromal cells from people with osteoporosis are fewer, and defective in both osteogenic and adipogenic capacity

Aim: Osteoporosis (OP) is caused by imbalanced bone remodelling homeostasis. It is highly prevalent, especially in post-menopausal women, resulting in high risk of fracture and morbidity. Mesenchymal stromal cells (MSCs) are osteoblast progenitors, and orchestrate the function of surrounding cells i...

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Main Authors: Féaron C. Cassidy, Ciara Shortiss, Kerry Thompson, Ana Soriano Arroquia, Colin G. Murphy, Stephen R. Kearns, William Curtin, Katarzyna Goljanek-Whysall, Timothy O’Brien, Cynthia M. Coleman
Format: Article
Language:English
Published: Open Exploration Publishing Inc. 2024-06-01
Series:Exploration of Musculoskeletal Diseases
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Online Access:https://www.explorationpub.com/uploads/Article/A100746/100746.pdf
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author Féaron C. Cassidy
Ciara Shortiss
Kerry Thompson
Ana Soriano Arroquia
Colin G. Murphy
Stephen R. Kearns
William Curtin
Katarzyna Goljanek-Whysall
Timothy O’Brien
Cynthia M. Coleman
author_facet Féaron C. Cassidy
Ciara Shortiss
Kerry Thompson
Ana Soriano Arroquia
Colin G. Murphy
Stephen R. Kearns
William Curtin
Katarzyna Goljanek-Whysall
Timothy O’Brien
Cynthia M. Coleman
author_sort Féaron C. Cassidy
collection DOAJ
description Aim: Osteoporosis (OP) is caused by imbalanced bone remodelling homeostasis. It is highly prevalent, especially in post-menopausal women, resulting in high risk of fracture and morbidity. Mesenchymal stromal cells (MSCs) are osteoblast progenitors, and orchestrate the function of surrounding cells including osteoblasts. Understanding MSC phenotype and function is therefore critical in discerning the aetiology of OP and developing superior therapies. Currently, adequate long-term therapeutic strategies are not available. Methods: Bioinformatic analysis of ribonucleic acid sequencing (RNA-seq) data revealed differential expression of genes primarily related to osteogenic differentiation and proliferation, followed by confirmatory in vitro analysis. Results: This study identified novel and previously proposed targets for therapeutic intervention in OP. Functional assessment demonstrated reduced MSC number and osteogenic capacity associated with OP. Proliferation was not affected but OP was unexpectedly associated with a reduction in MSC adipogenic differentiation capacity, correlating with donor age. Conclusions: These data indicate specific targets for further studies of future treatments for OP, including the assessment of modified MSCs as therapeutics. Advances in this area may contribute to reducing fracture-associated morbidity and mortality, and improving quality of life for the 200 million people living with OP globally.
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spelling doaj-art-cf008f6ffae74bf68e3eddaaaacf7ead2025-08-20T03:58:40ZengOpen Exploration Publishing Inc.Exploration of Musculoskeletal Diseases2836-64682024-06-012316418010.37349/emd.2024.00046Mesenchymal stromal cells from people with osteoporosis are fewer, and defective in both osteogenic and adipogenic capacityFéaron C. Cassidy0https://orcid.org/0000-0003-2577-9519Ciara Shortiss1https://orcid.org/0000-0002-2936-3310Kerry Thompson2https://orcid.org/0000-0003-2721-8977Ana Soriano Arroquia3https://orcid.org/0000-0003-2331-0899Colin G. Murphy4https://orcid.org/0000-0003-4533-8120Stephen R. Kearns5https://orcid.org/0000-0003-2355-739XWilliam Curtin6Katarzyna Goljanek-Whysall7https://orcid.org/0000-0001-8166-8800Timothy O’Brien8https://orcid.org/0000-0001-9028-5481Cynthia M. Coleman9https://orcid.org/0000-0003-0599-3948School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, D02 YN77 Dublin, IrelandCollege of Medicine, Nursing and Health Science, School of Medicine, Regenerative Medicine Institute, University of Galway, H91 FD82 Galway, IrelandCollege of Medicine, Nursing and Health Science, School of Medicine, Anatomy Imaging and Microscopy, University of Galway, H91 W5P7 Galway, IrelandInstitute of Ageing and Chronic Disease, University of Liverpool, L69 3BX Liverpool, UK; Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, Bonn, GermanyDepartment of Trauma and Orthopaedics, Galway University Hospitals, H91 YR71 Galway, IrelandDepartment of Trauma and Orthopaedics, Galway University Hospitals, H91 YR71 Galway, IrelandDepartment of Trauma and Orthopaedics, Galway University Hospitals, H91 YR71 Galway, IrelandInstitute of Ageing and Chronic Disease, University of Liverpool, L69 3BX Liverpool, UK; Department of Physiology, School of Medicine, University of Galway, H91 TK33 Galway, IrelandCollege of Medicine, Nursing and Health Science, School of Medicine, Regenerative Medicine Institute, University of Galway, H91 FD82 Galway, Ireland; Saolta University Healthcare Group, Galway University Hospitals, H91 YR71 Galway, Ireland; CÚRAM Centre for Research in Medical Devices, College of Medicine, Nursing and Health Sciences, School of Medicine, University of Galway, H91 FD82 Galway, IrelandCollege of Medicine, Nursing and Health Science, School of Medicine, Regenerative Medicine Institute, University of Galway, H91 FD82 Galway, IrelandAim: Osteoporosis (OP) is caused by imbalanced bone remodelling homeostasis. It is highly prevalent, especially in post-menopausal women, resulting in high risk of fracture and morbidity. Mesenchymal stromal cells (MSCs) are osteoblast progenitors, and orchestrate the function of surrounding cells including osteoblasts. Understanding MSC phenotype and function is therefore critical in discerning the aetiology of OP and developing superior therapies. Currently, adequate long-term therapeutic strategies are not available. Methods: Bioinformatic analysis of ribonucleic acid sequencing (RNA-seq) data revealed differential expression of genes primarily related to osteogenic differentiation and proliferation, followed by confirmatory in vitro analysis. Results: This study identified novel and previously proposed targets for therapeutic intervention in OP. Functional assessment demonstrated reduced MSC number and osteogenic capacity associated with OP. Proliferation was not affected but OP was unexpectedly associated with a reduction in MSC adipogenic differentiation capacity, correlating with donor age. Conclusions: These data indicate specific targets for further studies of future treatments for OP, including the assessment of modified MSCs as therapeutics. Advances in this area may contribute to reducing fracture-associated morbidity and mortality, and improving quality of life for the 200 million people living with OP globally.https://www.explorationpub.com/uploads/Article/A100746/100746.pdfosteoporosismesenchymal stromal cellmesenchymal stem cellbone marrow stromal cellsosteogenesisdifferentiation
spellingShingle Féaron C. Cassidy
Ciara Shortiss
Kerry Thompson
Ana Soriano Arroquia
Colin G. Murphy
Stephen R. Kearns
William Curtin
Katarzyna Goljanek-Whysall
Timothy O’Brien
Cynthia M. Coleman
Mesenchymal stromal cells from people with osteoporosis are fewer, and defective in both osteogenic and adipogenic capacity
Exploration of Musculoskeletal Diseases
osteoporosis
mesenchymal stromal cell
mesenchymal stem cell
bone marrow stromal cells
osteogenesis
differentiation
title Mesenchymal stromal cells from people with osteoporosis are fewer, and defective in both osteogenic and adipogenic capacity
title_full Mesenchymal stromal cells from people with osteoporosis are fewer, and defective in both osteogenic and adipogenic capacity
title_fullStr Mesenchymal stromal cells from people with osteoporosis are fewer, and defective in both osteogenic and adipogenic capacity
title_full_unstemmed Mesenchymal stromal cells from people with osteoporosis are fewer, and defective in both osteogenic and adipogenic capacity
title_short Mesenchymal stromal cells from people with osteoporosis are fewer, and defective in both osteogenic and adipogenic capacity
title_sort mesenchymal stromal cells from people with osteoporosis are fewer and defective in both osteogenic and adipogenic capacity
topic osteoporosis
mesenchymal stromal cell
mesenchymal stem cell
bone marrow stromal cells
osteogenesis
differentiation
url https://www.explorationpub.com/uploads/Article/A100746/100746.pdf
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