title: Osteoclasts are dispensable for hematopoietic stem cell maintenance and mobilization.
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.
authors: Department of Orthopedic Surgery, Keio Kanrinmaru Project, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors: Kana
authors: K
authors: Miyamoto
authors: Shigeyuki
authors: S
authors: Yoshida
authors: Miyuri
authors: M
authors: Kawasumi
authors: Kazuaki
authors: K
authors: Hashimoto
authors: Tokuhiro
authors: T
authors: Kimura
authors: Yuiko
authors: Y
authors: Sato
authors: Tami
authors: T
authors: Kobayashi
authors: Yoshiteru
authors: Y
authors: Miyauchi
authors: Hiroko
authors: H
authors: Hoshi
authors: Ryotaro
authors: R
authors: Iwasaki
authors: Hiroya
authors: H
authors: Miyamoto
authors: Wu
authors: W
authors: Hao
authors: Hideo
authors: H
authors: Morioka
authors: Kazuhiro
authors: K
authors: Chiba
authors: Takashi
authors: T
authors: Kobayashi
authors: Hisataka
authors: H
authors: Yasuda
authors: Josef M
authors: JM
authors: Penninger
authors: Yoshiaki
authors: Y
authors: Toyama
authors: Toshio
authors: T
authors: Suda
authors: Takeshi
authors: T
authors: Miyamoto
mesh_terms: D019386:Alendronate / Q000494:pharmacology; D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D001853:Bone Marrow / Q000378:metabolism; D002478:Cells, Cultured; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010022:Osteopetrosis / Q000473:pathology / Q000503:physiopathology; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D055153:Stem Cell Niche
chemical_list: D050071:Bone Density Conservation Agents; D053244:Osteoprotegerin; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; D016179:Granulocyte Colony-Stimulating Factor; D019386:Alendronate