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J Exp Med. 2011 Oct 24;208(11):2175-81. doi: 10.1084/jem.20101890. Epub 2011 Oct 17.

Osteoclasts are dispensable for hematopoietic stem cell maintenance and mobilization.

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1
Department of Orthopedic Surgery, Keio Kanrinmaru Project, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.

Erratum in

  • J Exp Med. 2011 Dec 19;208(13):2761. Dosage error in article text.

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.

PMID:
22006978
PMCID:
PMC3201203
DOI:
10.1084/jem.20101890
[Indexed for MEDLINE]
Free PMC Article
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