Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells - PubMed (original) (raw)

doi: 10.1038/nm1417. Epub 2006 May 21.

Ayelet Dar, Shoham Shivtiel, Alexander Kalinkovich, Kfir Lapid, Yejezkel Sztainberg, Melania Tesio, Robert M Samstein, Polina Goichberg, Asaf Spiegel, Ari Elson, Tsvee Lapidot

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Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells

Orit Kollet et al. Nat Med. 2006 Jun.

Abstract

Here we investigated the potential role of bone-resorbing osteoclasts in homeostasis and stress-induced mobilization of hematopoietic progenitors. Different stress situations induced activity of osteoclasts (OCLs) along the stem cell-rich endosteum region of bone, secretion of proteolytic enzymes and mobilization of progenitors. Specific stimulation of OCLs with RANKL recruited mainly immature progenitors to the circulation in a CXCR4- and MMP-9-dependent manner; however, RANKL did not induce mobilization in young female PTPepsilon-knockout mice with defective OCL bone adhesion and resorption. Inhibition of OCLs with calcitonin reduced progenitor egress in homeostasis, G-CSF mobilization and stress situations. RANKL-stimulated bone-resorbing OCLs also reduced the stem cell niche components SDF-1, stem cell factor (SCF) and osteopontin along the endosteum, which was associated with progenitor mobilization. Finally, the major bone-resorbing proteinase, cathepsin K, also cleaved SDF-1 and SCF. Our findings indicate involvement of OCLs in selective progenitor recruitment as part of homeostasis and host defense, linking bone remodeling with regulation of hematopoiesis.

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