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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.

Original publication

DOI

10.1084/jem.20110994

Type

Journal article

Journal

J Exp Med

Publication Date

12/03/2012

Volume

209

Pages

537 - 549

Keywords

Animals, Base Sequence, Bone Marrow Cells, Cell Differentiation, Cell Movement, DNA Primers, Female, Hematopoiesis, Hematopoietic Stem Cells, Mesenchymal Stem Cells, Mice, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Mutant Strains, Mice, Transgenic, Osteoblasts, Osteoclasts, Osteogenesis, Osteopetrosis, Phenotype, Pregnancy, Stem Cell Niche, Vacuolar Proton-Translocating ATPases