Osteoclasts are dispensable for hematopoietic stem cell maintenance and mobilization

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

doi:10.1084/jem.20101890

Cited by 133 publications

(58 citation statements)

References 36 publications

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“…Specifically, MΦ have been known to mediate HP retention in the BM (Casanova-Acebes et al, 2013; Chow et al, 2011). It has been shown that depletion of BM MΦ, but not other lineage-related cells such as osteoclasts (Miyamoto et al, 2011), is adequate to suppress endosteal Ob, inhibit the expression of HP-supportive cytokines at the endosteum, and elicit HP mobilization into the PB (Winkler et al, 2010). The content of MΦ in contact with Ob in the trabecular and endosteal lining of BM from Wt HM and p62 −/− HM mice was similar (Figs.…”

Section: Resultsmentioning

confidence: 99%

“…IκB kinase (IKK)-dependent NF-κB activation is essential for the bone remodeling function of osteoclasts (Ruocco et al, 2005), and gain-of-function of NF-κB activity prevents Ob differentiation as demonstrated in mice deficient in IKK (Chang et al, 2009). Since osteoclasts may be dispensable for HP mobilization in vivo (Miyamoto et al, 2011), we analyzed whether NF-κB-dependent signaling in Ob correlates with HP egress. Histological analysis of active NF-κB p65 in endosteal and trabecular Ob showed increased NF-κB nuclear localization in p62 −/− Ob in vivo (Fig.…”

Section: Resultsmentioning

confidence: 99%

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p62 Is Required for Stem Cell/Progenitor Retention through Inhibition of IKK/NF-κB/Ccl4 Signaling at the Bone Marrow Macrophage-Osteoblast Niche

et al. 2014

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In the bone marrow (BM), hematopoietic progenitors (HP) reside in specific anatomical niches near osteoblasts (Ob), macrophages (MΦ) and other cells forming the BM microenvironment. A connection between immunosurveillance and traffic of HP has been demonstrated but the regulatory signals that instruct immune regulation on HP circulation are unknown. We discovered that the BM microenvironment deficiency of p62, an autophagy regulator and signal organizer, results in loss of autophagic repression of macrophage contact-dependent activation of Ob NF-κB signaling. Consequently, Ob p62-deficient mice lose bone, Ob Ccl4 expression and HP chemotaxis towards Cxcl12 resulting in egress of short-term hematopoietic stem cells and myeloid progenitors. Finally, Ccl4 expression and myeloid progenitor egress are reversed by the deficiency of the p62 PB1 binding partner Nbr1. A functional ‘MΦ-Ob niche’ is required for myeloid progenitor/short-term stem cell retention, in which Ob p62 is required to maintain NF-κB signaling repression, osteogenesis and BM progenitor retention.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

p62 Is Required for Stem Cell/Progenitor Retention through Inhibition of IKK/NF-κB/Ccl4 Signaling at the Bone Marrow Macrophage-Osteoblast Niche

et al. 2014

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“…Inhibition of osteoclast activity with bisphosphonate treatment is associated with a modest increase in HSPC mobilization by G-CSF. 7,10 Moreover, Miyamoto and colleagues showed that in several transgenic mouse lines with impaired osteoclast activity (specifically, Csf1 , Fos , or Rankl deficient mice) G-CSF-induced HSPC mobilization is increased. 10 Each of these studies has certain limitations.…”

Section: Introductionmentioning

confidence: 99%

Osteoclasts are dispensable for hematopoietic progenitor mobilization by granulocyte colony-stimulating factor in mice

Rao

Supakorndej

Schmidt

et al. 2015

Experimental Hematology

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The contribution of osteoclasts to hematopoietic stem/progenitor cell (HSPC) retention in the bone marrow is controversial. Studies of HSPC trafficking in osteoclast-deficient mice are limited by osteopetrosis. Here, we employed two non-osteopetrotic mouse models to assess the contribution of osteoclasts to basal and granulocyte colony-stimulating factor (G-CSF) induced HSPC mobilization. We generated Rank−/− fetal liver chimeras using Csf3r−/− recipients to produce mice lacking G-CSF receptor expression in osteoclasts. Basal and G-CSF-induced HSPC mobilization was normal in these chimeras. We next acutely depleted osteoclasts in wild-type mice using the RANK ligand inhibitor osteoprotegerin (OPG). Marked suppression of osteoclasts was observed after a single injection of OPG-Fc. Basal and G-CSF-induced HSPC mobilization in OPG-Fc treated mice were comparable to control mice. Together, these data show that osteoclasts are not required for the efficient retention of HSPCs in the bone marrow and are dispensable for HSPC mobilization by G-CSF.

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“…Furthermore, impairment of osteoclast function by bisphosphonates reduces HSC number in bone marrow [95] and abolishes the HSC increment induced by PTH. Granulocyte-colony stimulating factor (G-CSF) administration increases bone resorption concomitant to the egress of HSCs, and antiosteoclastic agents, such as bisphosphonates or anti-RANKL antibody, increase the number of HSC mobilized from bone marrow [96][97][98]. The number of HSCs mobilized into the blood is higher in mice with osteopetrotic genotypes, including the M-CSF, the RANKL-and the c-Fos-deficient mice, and lower in mice lacking the anti-osteoclastogenic cytokine, OPG [98].…”

Section: Regulation Of Hematopoiesismentioning

confidence: 99%

Reprint of: The Great Beauty of the osteoclast

Cappariello

Maurizi

Veeriah

et al. 2014

Archives of Biochemistry and Biophysics

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Osteoclasts are dispensable for hematopoietic stem cell maintenance and mobilization

Abstract: The mobilization of hematopoietic stem cells does not require osteoclasts, which may even have an inhibitory effect.

Cited by 133 publications

References 36 publications

p62 Is Required for Stem Cell/Progenitor Retention through Inhibition of IKK/NF-κB/Ccl4 Signaling at the Bone Marrow Macrophage-Osteoblast Niche

p62 Is Required for Stem Cell/Progenitor Retention through Inhibition of IKK/NF-κB/Ccl4 Signaling at the Bone Marrow Macrophage-Osteoblast Niche

Osteoclasts are dispensable for hematopoietic progenitor mobilization by granulocyte colony-stimulating factor in mice

Reprint of: The Great Beauty of the osteoclast

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