Roles of osteoclasts in the control of medullary hematopoietic niches

Blin-Wakkach, Claudine; Rouleau, Matthieu; Wakkach, Abdelilah

doi:10.1016/j.abb.2014.06.032

Cited by 24 publications

(21 citation statements)

References 168 publications

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“…Restoring BM niches and HSC function by rescue of osteoclast activity demonstrates that osteoclasts are required for normal formation of HSC niches in newborn mice. 60,129 …”

Section: Bone Remodeling and Hemostasis Cross Talk Modulates Hsc Mainmentioning

confidence: 99%

“…Restoring BM niches and HSC function by rescue of osteoclast activity demonstrates that osteoclasts are required for normal formation of HSC niches in newborn mice. 60,129 Bone resorption is accompanied by extensive activity of osteoclast-secreted degrading enzymes, among which cathepsin K is essential. We have previously shown that cathepsin K cleaves endosteal membrane-bound stem cell factor, CXCL12, and osteopontin, all essential components of BM HSC niches with major stem cell-regulation activities.…”

Section: Bone Remodeling and Hemostasis Cross Talk Modulates Hsc Mainmentioning

confidence: 99%

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Regulation of long‐term repopulating hematopoietic stem cells by EPCR/PAR1 signaling

Gur-Cohen

Graf

Esmon

et al. 2016

Annals of the New York Academy of Sciences

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The common developmental origin of endothelial and hematopoietic cells is manifested by coexpression of several cell surface receptors. Adult murine bone marrow (BM) long-term repopulating hematopoietic stem cells (LT-HSCs), endowed with the highest repopulation and self-renewal potential, express endothelial protein C receptor (EPCR), which is used as a marker to isolate them. EPCR/PAR1 signaling in endothelial cells has anticoagulant and anti-inflammatory roles, while thrombin/PAR1 signaling induces coagulation and inflammation. Recent studies define two new PAR1-mediated signaling cascades that regulate EPCR+ LT-HSC BM retention and egress. EPCR/PAR1 signaling facilitates LT-HSC BM repopulation, retention, survival, and chemotherapy resistance by restricting nitric oxide (NO) production, maintaining NOlow LT-HSC BM retention with increased VLA4 expression, affinity, and adhesion. Conversely, acute stress and clinical mobilization upregulate thrombin generation and activate different PAR1 signaling which overcomes BM EPCR+ LT-HSC retention, inducing their recruitment to the bloodstream. Thrombin/PAR1 signaling induces NO generation, TACE-mediated EPCR shedding, and upregulation of CXCR4 and PAR1, leading to CXCL12-mediated stem and progenitor cell mobilization. This review discusses new roles for factors traditionally viewed as coagulation related, which independently act in the BM to regulate PAR1 signaling in bone- and blood-forming progenitor cells, navigating their fate by controlling NO production.

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“…Restoring BM niches and HSC function by rescue of osteoclast activity demonstrates that osteoclasts are required for normal formation of HSC niches in newborn mice. 60,129 …”

Section: Bone Remodeling and Hemostasis Cross Talk Modulates Hsc Mainmentioning

confidence: 99%

Section: Bone Remodeling and Hemostasis Cross Talk Modulates Hsc Mainmentioning

confidence: 99%

Regulation of long‐term repopulating hematopoietic stem cells by EPCR/PAR1 signaling

Gur-Cohen

Graf

Esmon

et al. 2016

Annals of the New York Academy of Sciences

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“…The majority of ARO patients have high frequencies of circulating CD34+ cells, because of the limited BM cavities and the reduction of hematopoietic stem cell (HSC) niches 16,17 . Of note, previous studies showed that peripheral blood of osteopetrotic patients is highly enriched in cells with myeloid and erythroid clonogenic potential circulate 16,18 .…”

Section: Introductionmentioning

confidence: 99%

Expanded circulating hematopoietic stem/progenitor cells as novel cell source for the treatment of TCIRG1 osteopetrosis

et al. 2020

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“…The physiologic lineage commitment of monocyte‐macrophage precursor cells is pivotal to maintain skeletal homeostasis. Deregulated OC differentiation, recruitment, and/or function can result in either osteoporosis or osteopetrosis, affecting not only the skeleton but also altering the bone marrow niche . The cytokines macrophage–colony stimulating factor (M‐CSF) and receptor activator of nuclear factor κB ligand (RANKL) are indispensable for macrophage and OC development, respectively.…”

Section: Introductionmentioning

confidence: 99%

“…Deregulated OC differentiation, recruitment, and/or function can result in either osteoporosis or osteopetrosis, (2,3) affecting not only the skeleton but also altering the bone marrow niche. (4)(5)(6) The cytokines macrophage-colony stimulating factor (M-CSF) (7) and receptor activator of nuclear factor kB ligand (RANKL) (8,9) are indispensable for macrophage and OC development, respectively. Op/op mice lacking M-CSF exhibit severe osteopetrosis due to an absence of both OCs and macrophages.…”

Section: Introductionmentioning

confidence: 99%

Nf1 Haploinsufficiency Alters Myeloid Lineage Commitment and Function, Leading to Deranged Skeletal Homeostasis

Rhodes

Yang

Dong

et al. 2015

Journal of Bone and Mineral Research

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While nullizygous loss of NF1 leads to myeloid malignancies, haploinsufficient loss of NF1 (Nf1) has been shown to contribute to osteopenia and osteoporosis which occurs in approximately 50 percent of neurofibromatosis type 1 (NF1) patients. Bone marrow mononuclear cells of haploinsufficient NF1 patients and Nf1+/- mice exhibit increased osteoclastogenesis and accelerated bone turnover, however the culprit hematopoietic lineages responsible for perpetuating these osteolytic manifestations have yet to be elucidated. Here we demonstrate that conditional inactivation of a single Nf1 allele within the myeloid progenitor cell population (Nf1-LysM) is necessary and sufficient to promote multiple osteoclast gain-in-functions, resulting in enhanced osteoclastogenesis and accelerated osteoclast bone lytic activity in response to pro-resorptive challenge in vivo. Surprisingly, mice conditionally Nf1 heterozygous in mature, terminally differentiated osteoclasts (Nf1-Ctsk) do not exhibit any of these skeletal phenotypes, indicating a critical requirement for Nf1 haploinsufficiency at a more primitive/progenitor stage of myeloid development in perpetuating osteolytic activity. We further identified p21Ras dependent hyper-phosphorylation of Pu.1 within the nucleus of Nf1 haploinsufficent myelomoncytic osteoclast precursors, providing a novel therapeutic target for the potential treatment of NF1 associated osteolytic manifestations.

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Roles of osteoclasts in the control of medullary hematopoietic niches

Cited by 24 publications

References 168 publications

Regulation of long‐term repopulating hematopoietic stem cells by EPCR/PAR1 signaling

Regulation of long‐term repopulating hematopoietic stem cells by EPCR/PAR1 signaling

Expanded circulating hematopoietic stem/progenitor cells as novel cell source for the treatment of TCIRG1 osteopetrosis

Nf1 Haploinsufficiency Alters Myeloid Lineage Commitment and Function, Leading to Deranged Skeletal Homeostasis

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