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Osteoclasts are not crucial for hematopoietic stem cell maintenance in adult mice

Flores Bjurström, Carmen LU ; Moscatelli, Ilana LU ; Thudium, Christian LU ; Gudmann, Natasja Staehr ; Thomsen, Jesper S. ; Bruel, Annemarie ; Karsdal, Morten A. ; Henriksen, Kim and Richter, Johan LU (2013) In Haematologica 98(12). p.1848-1855
Abstract
The osteoclast is vital for establishment of normal hematopoiesis in the developing animal. However, its role for maintenance of hematopoiesis in adulthood is more controversial. To shed more light on this process, we transplanted hematopoietic stem cells from two osteopetrotic mouse models, with lack of osteoclasts or defective osteoclast function, to normal adult mice and examined the bone phenotype and hematopoiesis in the recipients. B6SJL mice were lethally irradiated and subsequently transplanted with oc/oc, Receptor Activator of Nuclear Factor Kappa B knockout or control fetal liver cells. Osteoclasts derived from the recipient animals were tested in vitro for osteoclastogenesis and resorptive function. Bone remodeling changes were... (More)
The osteoclast is vital for establishment of normal hematopoiesis in the developing animal. However, its role for maintenance of hematopoiesis in adulthood is more controversial. To shed more light on this process, we transplanted hematopoietic stem cells from two osteopetrotic mouse models, with lack of osteoclasts or defective osteoclast function, to normal adult mice and examined the bone phenotype and hematopoiesis in the recipients. B6SJL mice were lethally irradiated and subsequently transplanted with oc/oc, Receptor Activator of Nuclear Factor Kappa B knockout or control fetal liver cells. Osteoclasts derived from the recipient animals were tested in vitro for osteoclastogenesis and resorptive function. Bone remodeling changes were assessed using biomarkers of bone tumrnover and micro-CT. Hematopoiesis was assessed by flow cytometry and colony formation, and hematopoietic stem cell function by secondary competitive transplantations and cell cycle analysis. After transplantation, a donor chimerism of 97-98% was obtained, and by 15 weeks mild osteopetrosis had developed in recipients of cells from osteopetrotic mice. There were no alterations in the number of bone marrow cells. Colony formation was slightly reduced in Receptor Activator of Nuclear Factor Kappa B knock-out recipients but unchanged in oc/oc recipients. Phenotypically, stem cells were marginally reduced in recipients of cells from osteopetrotic mice, but no significant difference was seen in cell cycle status and in competitive secondary transplantations all three groups performed equally well. Our results indicate that osteoclast function is not crucial for hematopoietic stem cell maintenance in adult mice. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
in
Haematologica
volume
98
issue
12
pages
1848 - 1855
publisher
Ferrata Storti Foundation
external identifiers
  • wos:000328545500012
  • scopus:84889804765
  • pmid:24097632
ISSN
1592-8721
DOI
10.3324/haematol.2013.089466
language
English
LU publication?
yes
id
d85faea5-8b44-445d-aade-40ac81ea4a97 (old id 4269073)
date added to LUP
2016-04-01 12:53:23
date last changed
2020-05-20 02:00:09
@article{d85faea5-8b44-445d-aade-40ac81ea4a97,
  abstract     = {The osteoclast is vital for establishment of normal hematopoiesis in the developing animal. However, its role for maintenance of hematopoiesis in adulthood is more controversial. To shed more light on this process, we transplanted hematopoietic stem cells from two osteopetrotic mouse models, with lack of osteoclasts or defective osteoclast function, to normal adult mice and examined the bone phenotype and hematopoiesis in the recipients. B6SJL mice were lethally irradiated and subsequently transplanted with oc/oc, Receptor Activator of Nuclear Factor Kappa B knockout or control fetal liver cells. Osteoclasts derived from the recipient animals were tested in vitro for osteoclastogenesis and resorptive function. Bone remodeling changes were assessed using biomarkers of bone tumrnover and micro-CT. Hematopoiesis was assessed by flow cytometry and colony formation, and hematopoietic stem cell function by secondary competitive transplantations and cell cycle analysis. After transplantation, a donor chimerism of 97-98% was obtained, and by 15 weeks mild osteopetrosis had developed in recipients of cells from osteopetrotic mice. There were no alterations in the number of bone marrow cells. Colony formation was slightly reduced in Receptor Activator of Nuclear Factor Kappa B knock-out recipients but unchanged in oc/oc recipients. Phenotypically, stem cells were marginally reduced in recipients of cells from osteopetrotic mice, but no significant difference was seen in cell cycle status and in competitive secondary transplantations all three groups performed equally well. Our results indicate that osteoclast function is not crucial for hematopoietic stem cell maintenance in adult mice.},
  author       = {Flores Bjurström, Carmen and Moscatelli, Ilana and Thudium, Christian and Gudmann, Natasja Staehr and Thomsen, Jesper S. and Bruel, Annemarie and Karsdal, Morten A. and Henriksen, Kim and Richter, Johan},
  issn         = {1592-8721},
  language     = {eng},
  number       = {12},
  pages        = {1848--1855},
  publisher    = {Ferrata Storti Foundation},
  series       = {Haematologica},
  title        = {Osteoclasts are not crucial for hematopoietic stem cell maintenance in adult mice},
  url          = {http://dx.doi.org/10.3324/haematol.2013.089466},
  doi          = {10.3324/haematol.2013.089466},
  volume       = {98},
  year         = {2013},
}