Osteoclasts promote the formation of hematopoietic stem cell niches in the bone marrow

Author:

Mansour Anna12,Abou-Ezzi Grazia13,Sitnicka Ewa4,W. Jacobsen Sten Eirik45,Wakkach Abdelilah13,Blin-Wakkach Claudine13

Affiliation:

1. Université de Nice Sophia Antipolis, 06000 Nice, France

2. Centre National de la Recherche Scientifique, UMR 6235, Faculté de Médecine, 06100 Nice, France

3. Institut National de la Santé et de la Recherche Médicale, UMR 576, Hôpital de l’Archet, 06202 Nice, France

4. Hematopoietic Stem Cell Laboratory, Lund Research Center for Stem Cell Biology and Cell Therapy, Lund University, 22184 Lund, Sweden

5. Haematopoietic Stem Cell Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, England, UK

Abstract

Formation of the hematopoietic stem cell (HSC) niche in bone marrow (BM) is tightly associated with endochondral ossification, but little is known about the mechanisms involved. We used the oc/oc mouse, a mouse model with impaired endochondral ossification caused by a loss of osteoclast (OCL) activity, to investigate the role of osteoblasts (OBLs) and OCLs in the HSC niche formation. The absence of OCL activity resulted in a defective HSC niche associated with an increased proportion of mesenchymal progenitors but reduced osteoblastic differentiation, leading to impaired HSC homing to the BM. Restoration of OCL activity reversed the defect in HSC niche formation. Our data demonstrate that OBLs are required for establishing HSC niches and that osteoblastic development is induced by OCLs. These findings broaden our knowledge of the HSC niche formation, which is critical for understanding normal and pathological hematopoiesis.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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