Mesenchymal stromal cells from people with osteoporosis are fewer, and defective in both osteogenic and adipogenic capacity
Cassidy, Féaron C. Shortiss, Ciara Thompson, Kerry Soriano Arroquia, Ana Murphy, Colin G. Kearns, Stephen R. Curtin, William Goljanek-Whysal, Katarzyna O'Brien, Timothy Coleman, Cynthia M.
Cassidy, Féaron C.
Shortiss, Ciara
Thompson, Kerry
Soriano Arroquia, Ana
Murphy, Colin G.
Kearns, Stephen R.
Curtin, William
Goljanek-Whysal, Katarzyna
O'Brien, Timothy
Coleman, Cynthia M.
Repository DOI
Publication Date
2024-06-03
Type
journal article
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Citation
Cassidy, Féaron C., Shortiss, Ciara, Thompson, Kerry, Arroquia, Ana Soriano, Murphy, Colin G., Kearns, Stephen R., Curtin, William, Goljanek-Whysall, Katarzyna, O'Brien, Timothy, Coleman, Cynthia M. (2024). Mesenchymal stromal cells from people with osteoporosis are fewer, and defective in both osteogenic and adipogenic capacity. Exploration of Musculoskeletal Diseases, 2(3), 164-180. doi:10.37349/emd.2024.00046
Abstract
Introduction/Purpose: Osteoporosis is caused by imbalanced bone remodelling homeostasis. It is highly prevalent, especially in post-menopausal women, resulting in high risk of fracture and morbidity. 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 osteoporosis and developing superior therapies. Currently, adequate long-term therapeutic strategies are not available. Methods: Bioinformatic analysis of 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 (P2RY6, AJAP1, ARHGAP32, EPHB6, TEP1, HAUS5, WAVE and Reelin) and previously proposed targets (PRKG1, EFNB2, c-Fos, OXTR, SMOC1, NPR3 and TEP1) for therapeutic intervention in osteoporosis. Functional assessment demonstrated reduced MSC number and osteogenic capacity associated with osteoporosis. Proliferation was not affected but osteoporosis 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 osteoporosis, 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 osteoporosis globally.
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Publisher
Open Exploration
Publisher DOI
10.37349/emd.2024.00046
Rights
Attribution 4.0 International