title: Osteoclasts promote the formation of hematopoietic stem cell niches in the bone marrow.
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.
authors.affiliation: Université de Nice Sophia Antipolis, 06000 Nice, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Mansour
authors.forename: Grazia
authors.initials: G
authors.lastname: Abou-Ezzi
authors.forename: Ewa
authors.initials: E
authors.lastname: Sitnicka
authors.forename: Sten Eirik W
authors.initials: SE
authors.lastname: Jacobsen
authors.forename: Abdelilah
authors.initials: A
authors.lastname: Wakkach
authors.forename: Claudine
authors.initials: C
authors.lastname: Blin-Wakkach
mesh_terms: D000818:Animals; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006410:Hematopoiesis / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology; D010022:Osteopetrosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype; D011247:Pregnancy; D055153:Stem Cell Niche / Q000502:physiology*; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics / Q000502:physiology
chemical_list: C484226:Atp6ap1 protein, mouse; D017931:DNA Primers; D025262:Vacuolar Proton-Translocating ATPases