Osteoclasts are dispensable for hematopoietic stem cell maintenance and mobilization

Kana Miyamoto, Shigeyuki Yoshida, Miyuri Kawasumi, Kazuaki Hashimoto, Tokuhiro Kimura, Yuiko Sato, Tami Kobayashi, Yoshiteru Miyauchi, Hiroko Hoshi, Ryotaro Iwasaki, Hiroya Miyamoto, Wu Hao, Hideo Morioka, Kazuhiro Chiba, Takashi Kobayashi, Hisataka Yasuda, Josef M. Penninger, Yoshiaki Toyama, Toshio Suda, Takeshi Miyamoto

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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, osteoprotegerindeficient 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.

Original languageEnglish
Pages (from-to)2175-2181
Number of pages7
JournalJournal of Experimental Medicine
Volume208
Issue number11
DOIs
Publication statusPublished - 2011 Oct 24

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Miyamoto, K., Yoshida, S., Kawasumi, M., Hashimoto, K., Kimura, T., Sato, Y., Kobayashi, T., Miyauchi, Y., Hoshi, H., Iwasaki, R., Miyamoto, H., Hao, W., Morioka, H., Chiba, K., Kobayashi, T., Yasuda, H., Penninger, J. M., Toyama, Y., Suda, T., & Miyamoto, T. (2011). Osteoclasts are dispensable for hematopoietic stem cell maintenance and mobilization. Journal of Experimental Medicine, 208(11), 2175-2181. https://doi.org/10.1084/jem.20101890