Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells

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

Research output: Contribution to journalArticlepeer-review

654 Scopus citations

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 PTPε-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.

Original languageEnglish
Pages (from-to)657-664
Number of pages8
JournalNature Medicine
Volume12
Issue number6
DOIs
StatePublished - Jun 2006
Externally publishedYes

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