Osteoclasts are dispensable for hematopoietic stem cell maintenance and mobilization
Open Access
- 17 October 2011
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 208 (11), 2175-2181
- https://doi.org/10.1084/jem.20101890
Abstract
Hematopoietic stem cells (HSCs) are maintained in a specific bone marrow (BM) niche in cavities formed by osteoclasts. Osteoclast-deficient mice are osteopetrotic and exhibit closed BM cavities. Osteoclast activity is inversely correlated with hematopoietic activity; however, how osteoclasts and the BM cavity potentially regulate hematopoiesis is not well understood. To investigate this question, we evaluated hematopoietic activity in three osteopetrotic mouse models: op/op, c-Fos-deficient, and RANKL (receptor activator of nuclear factor kappa B ligand)-deficient mice. We show that, although osteoclasts and, by consequence, BM cavities are absent in these animals, hematopoietic stem and progenitor cell (HSPC) mobilization after granulocyte colony-stimulating factor injection was comparable or even higher in all three lines compared with wild-type mice. In contrast, osteoprotegerin-deficient mice, which have increased numbers of osteoclasts, showed reduced HSPC mobilization. BM-deficient patients and mice reportedly maintain hematopoiesis in extramedullary spaces, such as spleen; however, splenectomized op/op mice did not show reduced HSPC mobilization. Interestingly, we detected an HSC population in osteopetrotic bone of op/op mice, and pharmacological ablation of osteoclasts in wild-type mice did not inhibit, and even increased, HSPC mobilization. These results suggest that osteoclasts are dispensable for HSC mobilization and may function as negative regulators in the hematopoietic system.Keywords
This publication has 37 references indexed in Scilit:
- The HSC niche concept has turned 31Annals of the New York Academy of Sciences, 2010
- Effects of aging on hematopoietic stem and progenitor cellsCurrent Opinion in Immunology, 2009
- Granulocyte Colony-Stimulating Factor Induces Osteoblast Apoptosis and Inhibits Osteoblast DifferentiationJournal of Bone and Mineral Research, 2008
- Foxo3a Is Essential for Maintenance of the Hematopoietic Stem Cell PoolCell Stem Cell, 2007
- Osteoclasts: What Do They Do and How Do They Do It?The American Journal of Pathology, 2007
- Signals from the Sympathetic Nervous System Regulate Hematopoietic Stem Cell Egress from Bone MarrowCell, 2006
- Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool sizeThe Journal of Experimental Medicine, 2005
- Identification of the haematopoietic stem cell niche and control of the niche sizeNature, 2003
- Osteoblastic cells regulate the haematopoietic stem cell nicheNature, 2003
- Calcitonin receptor antibodies in the identification of osteoclastsBone, 1999