Osteoclasts Promote the Formation of Hematopoietic Stem Cell Niches in the Bone Marrow

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2012 Feb 22

PMID 22351931

Citations 104

Authors

Anna Mansour

Grazia Abou-Ezzi

Ewa Sitnicka

Sten Eirik W Jacobsen

Abdelilah Wakkach

Claudine Blin-Wakkach

Affiliations

Soon will be listed here.

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.

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References

Lotinun S, Evans G, Turner R, Oursler M . Deletion of membrane-bound steel factor results in osteopenia in mice. J Bone Miner Res. 2005; 20(4):644-52. DOI: 10.1359/JBMR.041209. View

Winkler I, Sims N, Pettit A, Barbier V, Nowlan B, Helwani F . Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs. Blood. 2010; 116(23):4815-28. DOI: 10.1182/blood-2009-11-253534. View

Mendez-Ferrer S, Michurina T, Ferraro F, Mazloom A, MacArthur B, Lira S . Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature. 2010; 466(7308):829-34. PMC: 3146551. DOI: 10.1038/nature09262. View

Cho K, Joo S, Han H, Ryu K, Woo S . Osteoclast activation by receptor activator of NF-kappaB ligand enhances the mobilization of hematopoietic progenitor cells from the bone marrow in acute injury. Int J Mol Med. 2010; 26(4):557-63. DOI: 10.3892/ijmm_00000499. View

Blin-Wakkach C, Wakkach A, Rochet N, Carle G . Characterization of a novel bipotent hematopoietic progenitor population in normal and osteopetrotic mice. J Bone Miner Res. 2004; 19(7):1137-43. DOI: 10.1359/JBMR.040318. View

Mansour A, Anginot A, Mancini S, Schiff C, Carle G, Wakkach A . Osteoclast activity modulates B-cell development in the bone marrow. Cell Res. 2011; 21(7):1102-15. PMC: 3193501. DOI: 10.1038/cr.2011.21. View

Calvi L, Adams G, Weibrecht K, Weber J, Olson D, Knight M . Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003; 425(6960):841-6. DOI: 10.1038/nature02040. View

Chan C, Chen C, Luppen C, Kim J, DeBoer A, Wei K . Endochondral ossification is required for haematopoietic stem-cell niche formation. Nature. 2008; 457(7228):490-4. PMC: 2648141. DOI: 10.1038/nature07547. View

Tagaya H, Kunisada T, Yamazaki H, Yamane T, Tokuhisa T, Wagner E . Intramedullary and extramedullary B lymphopoiesis in osteopetrotic mice. Blood. 2000; 95(11):3363-70. View

10.

Levesque J, Winkler I . Hierarchy of immature hematopoietic cells related to blood flow and niche. Curr Opin Hematol. 2011; 18(4):220-5. DOI: 10.1097/MOH.0b013e3283475fe7. View

11.

Martin T, Sims N . Osteoclast-derived activity in the coupling of bone formation to resorption. Trends Mol Med. 2005; 11(2):76-81. DOI: 10.1016/j.molmed.2004.12.004. View

12.

Seifert M, Marks Jr S . Morphological evidence of reduced bone resorption in the osteosclerotic (oc) mouse. Am J Anat. 1985; 172(2):141-53. DOI: 10.1002/aja.1001720204. View

13.

Banco R, Seifert M, Marks Jr S, Mcguire J . Rickets and osteopetrosis: the osteosclerotic (oc) mouse. Clin Orthop Relat Res. 1985; (201):238-46. View

14.

Kong Y, Yoshida H, Sarosi I, Tan H, Timms E, Capparelli C . OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. 1999; 397(6717):315-23. DOI: 10.1038/16852. View

15.

Blin-Wakkach C, Wakkach A, Quincey D, Carle G . Interleukin-7 partially rescues B-lymphopoiesis in osteopetrotic oc/oc mice through the engagement of B220+ CD11b+ progenitors. Exp Hematol. 2006; 34(7):851-9. DOI: 10.1016/j.exphem.2006.04.003. View

16.

Morikawa S, Mabuchi Y, Kubota Y, Nagai Y, Niibe K, Hiratsu E . Prospective identification, isolation, and systemic transplantation of multipotent mesenchymal stem cells in murine bone marrow. J Exp Med. 2009; 206(11):2483-96. PMC: 2768869. DOI: 10.1084/jem.20091046. View

17.

Levesque J, Helwani F, Winkler I . The endosteal 'osteoblastic' niche and its role in hematopoietic stem cell homing and mobilization. Leukemia. 2010; 24(12):1979-92. DOI: 10.1038/leu.2010.214. View

18.

Gattei V, Aldinucci D, Quinn J, Degan M, Cozzi M, Perin V . Human osteoclasts and preosteoclast cells (FLG 29.1) express functional c-kit receptors and interact with osteoblast and stromal cells via membrane-bound stem cell factor. Cell Growth Differ. 1996; 7(6):753-63. View

19.

Tang Y, Wu X, Lei W, Pang L, Wan C, Shi Z . TGF-beta1-induced migration of bone mesenchymal stem cells couples bone resorption with formation. Nat Med. 2009; 15(7):757-65. PMC: 2727637. DOI: 10.1038/nm.1979. View

20.

Sims N, Gooi J . Bone remodeling: Multiple cellular interactions required for coupling of bone formation and resorption. Semin Cell Dev Biol. 2008; 19(5):444-51. DOI: 10.1016/j.semcdb.2008.07.016. View