Cathepsin X is secreted by human osteoblasts, digests CXCL-12 and impairs adhesion of hematopoietic stem and progenitor cells to osteoblasts

Cathepsin X is secreted by human osteoblasts, digests CXCL-12 and impairs adhesion of hematopoietic stem and progenitor cells to osteoblasts

Author Staudt, Nicole D. Google Scholar
Aicher, Wilhelm K. Google Scholar
Kalbacher, Hubert Google Scholar
Stevanovic, Stefan Google Scholar
Carmona, Adriana Karaoglanovic Autor UNIFESP Google Scholar
Bogyo, Matthew Google Scholar
Klein, Gerd Google Scholar
Institution Univ Tubingen
Universidade Federal de São Paulo (UNIFESP)
Stanford Univ
Abstract Background Hematopoietic stem cells are retained within discrete bone marrow niches through the effects of cell adhesion molecules and chemokine gradients. However, a small proportion of hematopoietic stem cells can also be found trafficking in the peripheral blood. During induced stem cell mobilization a proteolytic microenvironment is generated, but whether proteases are also involved in physiological trafficking of hematopoietic stem cells is not known. in the present study we examined the expression, secretion and function of the cysteine protease cathepsin X by cells of the human bone marrow.Design and Methods Human osteoblasts, bone marrow stromal cells and hematopoietic stem and progenitor cells were analyzed for the secretion of cathepsin X by western blotting, active site labeling, immunofluorescence staining and activity assays. A possible involvement of cathepsin X in cell adhesion and CXCL-12-mediated cell migration was studied in functional assays. Matrix-assisted laser desorption and ionization time-of-flight (MALDI-TOF) analysis revealed the digestion mechanism of CXCL-12 by cathepsin X.Results Osteoblasts and stromal cells secrete cathepsin X, whereas hematopoietic stem and progenitor cells do not. Using a cathepsin X-selective substrate, we detected the catalytic activity of cathepsin X in cell culture supernatants of osteoblasts. Activated cathepsin X is able to reduce cellular adhesive interactions between CD34(+) hematopoietic stem and progenitor cells and adherent osteoblasts. the chemokine CXCL-12, a highly potent chemoattractant for hematopoietic stem cells secreted by osteoblasts, is readily digested by cathepsin X.Conclusions the exo-peptidase cathepsin X has been identified as a new member of the group of CXCL-12-degrading enzymes secreted by non-hematopoietic bone marrow cells. Functional data indicate that cathepsin X can influence hematopoietic stem and progenitor cell trafficking in the bone marrow.
Keywords stem cell niche
proteolytic microenvironment
proteases
cell adhesion
cysteine cathepsins
active site labeling
Language English
Sponsor Landesstiftung Baden-Wurttemberg gGmbH (Stuttgart, Germany)
Deutsche Forschungsgemeinschaft
NIH Roadmaps National Technology Centers for Networks and Pathways
Grant number Landesstiftung Baden-Wurttemberg gGmbH (Stuttgart, Germany): P-LS-AS/HSPA8-13
Deutsche Forschungsgemeinschaft: GK794
NIH Roadmaps National Technology Centers for Networks and Pathways: U54 RR020843
NIH Roadmaps National Technology Centers for Networks and Pathways: R01 EB 005011
Date 2010-09-01
Published in Haematologica-the Hematology Journal. Pavia: Ferrata Storti Foundation, v. 95, n. 9, p. 1452-1460, 2010.
ISSN 0390-6078 (Sherpa/Romeo, impact factor)
Publisher Ferrata Storti Foundation
Extent 1452-1460
Origin http://dx.doi.org/10.3324/haematol.2009.018671
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000281933200005
URI http://repositorio.unifesp.br/handle/11600/32856

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