Lymperi, Stefania, Ersek, Adel, Ferraro, Francesca, Dazzi, Francesco and Horwood, Nicole J ORCID: https://orcid.org/0000-0002-6344-1677
(2011)
Inhibition of osteoclast function reduces hematopoietic stem cell numbers in vivo.
Blood, 117 (5).
pp. 1540-1549.
ISSN 0006-4971
Abstract
Osteoblasts play a crucial role in the hematopoietic stem cell (HSC) niche; however, an overall increase in their number does not necessarily promote hematopoiesis. Because the activity of osteoblasts and osteoclasts is coordinately regulated, we hypothesized that active bone-resorbing osteoclasts would participate in HSC niche maintenance. Mice treated with bisphosphonates exhibited a decrease in proportion and absolute number of Lin(-)cKit(+)Sca1(+) Flk2(-) (LKS Flk2(-)) and long-term culture-initiating cells in bone marrow (BM). In competitive transplantation assays, the engraftment of treated BM cells was inferior to that of controls, confirming a decrease in HSC numbers. Accordingly, bisphosphonates abolished the HSC increment produced by parathyroid hormone. In contrast, the number of colony-forming-unit cells in BM was increased. Because a larger fraction of LKS in the BM of treated mice was found in the S/M phase of the cell cycle, osteoclast impairment makes a proportion of HSCs enter the cell cycle and differentiate. To prove that HSC impairment was a consequence of niche manipulation, a group of mice was treated with bisphosphonates and then subjected to BM transplantation from untreated donors. Treated recipient mice experienced a delayed hematopoietic recovery compared with untreated controls. Our findings demonstrate that osteoclast function is fundamental in the HSC niche.
Item Type: | Article |
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Uncontrolled Keywords: | animals,blotting, western,pharmacology,metabolism,bone marrow transplantation,etiology,physiology,cells, cultured,pharmacology,female,flow cytometry,metabolism,physiology,physiology,mice,mice, inbred c57bl,cytology,pharmacology,physiology,drug effects,physiology,tomography, x-ray computed |
Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health |
Depositing User: | LivePure Connector |
Date Deposited: | 06 Mar 2019 10:30 |
Last Modified: | 24 Jul 2024 09:49 |
URI: | https://ueaeprints.uea.ac.uk/id/eprint/70137 |
DOI: | 10.1182/blood-2010-05-282855 |
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