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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Carmen Flores Bjurström
  • Ilana Moscatelli
  • Christian Thudium
  • Natasja Staehr Gudmann
  • Jesper S. Thomsen
  • Annemarie Bruel
  • Morten A. Karsdal
  • Kim Henriksen
  • Johan Richter
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Hematology
Original languageEnglish
Pages (from-to)1848-1855
JournalHaematologica
Volume98
Issue number12
Publication statusPublished - 2013
Publication categoryResearch
Peer-reviewedYes