Inhibition of osteoclast function reduces hematopoietic stem cell numbers in vivo

Lymperi, Stefania, Ersek, Adel, Ferraro, Francesca, Dazzi, Francesco and Horwood, Nicole J (2011) Inhibition of osteoclast function reduces hematopoietic stem cell numbers in vivo. Blood, 117 (5). pp. 1540-1549. ISSN 0006-4971

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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
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
Depositing User: LivePure Connector
Date Deposited: 06 Mar 2019 10:30
Last Modified: 22 Apr 2020 07:34
URI: https://ueaeprints.uea.ac.uk/id/eprint/70137
DOI: 10.1182/blood-2010-05-282855

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