Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells

Nat Med. 2006 Jun;12(6):657-64. doi: 10.1038/nm1417. Epub 2006 May 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Resorption*
  • Bone and Bones / anatomy & histology*
  • Carrier Proteins / metabolism
  • Cathepsin K
  • Cathepsins / genetics
  • Cathepsins / metabolism
  • Cell Line
  • Cell Movement / physiology*
  • Chemokine CXCL12
  • Chemokines, CXC / metabolism
  • Female
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / physiology*
  • Homeostasis
  • Humans
  • Matrix Metalloproteinase 9 / metabolism
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Osteoclasts / cytology
  • Osteoclasts / metabolism*
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / metabolism
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptor-Like Protein Tyrosine Phosphatases, Class 4
  • Receptors, CXCR4 / metabolism
  • Stem Cell Factor / metabolism

Substances

  • CXCL12 protein, human
  • Carrier Proteins
  • Chemokine CXCL12
  • Chemokines, CXC
  • Cxcl12 protein, mouse
  • Membrane Glycoproteins
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, CXCR4
  • Stem Cell Factor
  • TNFRSF11A protein, human
  • TNFSF11 protein, human
  • Tnfrsf11a protein, mouse
  • Tnfsf11 protein, mouse
  • Protein Tyrosine Phosphatases
  • Ptpre protein, mouse
  • Receptor-Like Protein Tyrosine Phosphatases, Class 4
  • Cathepsins
  • CTSK protein, human
  • Cathepsin K
  • Ctsk protein, mouse
  • Matrix Metalloproteinase 9