Nature Medicine
- 12, 657 - 664 (2006)
Published online: 21 May 2006; | doi:10.1038/nm1417
Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cellsOrit Kollet1, Ayelet Dar1, Shoham Shivtiel1, Alexander Kalinkovich1, Kfir Lapid1, Yejezkel Sztainberg1, Melania Tesio1, Robert M Samstein1, Polina Goichberg1, Asaf Spiegel1, Ari Elson2 & Tsvee Lapidot11
Department of Immunology, Rehovot, 76100, Israel. 2
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel.
Correspondence should be addressed to Tsvee Lapidot Tsvee.Lapidot@weizmann.ac.il 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 PTP -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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