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

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dc.contributor.author Staudt, Nicole D.
dc.contributor.author Aicher, Wilhelm K.
dc.contributor.author Kalbacher, Hubert
dc.contributor.author Stevanovic, Stefan
dc.contributor.author Carmona, Adriana Karaoglanovic [UNIFESP]
dc.contributor.author Bogyo, Matthew
dc.contributor.author Klein, Gerd
dc.date.accessioned 2016-01-24T14:05:24Z
dc.date.available 2016-01-24T14:05:24Z
dc.date.issued 2010-09-01
dc.identifier http://dx.doi.org/10.3324/haematol.2009.018671
dc.identifier.citation Haematologica-the Hematology Journal. Pavia: Ferrata Storti Foundation, v. 95, n. 9, p. 1452-1460, 2010.
dc.identifier.issn 0390-6078
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/32856
dc.description.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. en
dc.description.sponsorship Landesstiftung Baden-Wurttemberg gGmbH (Stuttgart, Germany)
dc.description.sponsorship Deutsche Forschungsgemeinschaft
dc.description.sponsorship NIH Roadmaps National Technology Centers for Networks and Pathways
dc.format.extent 1452-1460
dc.language.iso eng
dc.publisher Ferrata Storti Foundation
dc.relation.ispartof Haematologica-the Hematology Journal
dc.rights Acesso aberto
dc.subject stem cell niche en
dc.subject proteolytic microenvironment en
dc.subject proteases en
dc.subject cell adhesion en
dc.subject cysteine cathepsins en
dc.subject active site labeling en
dc.title Cathepsin X is secreted by human osteoblasts, digests CXCL-12 and impairs adhesion of hematopoietic stem and progenitor cells to osteoblasts en
dc.type Artigo
dc.contributor.institution Univ Tubingen
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Stanford Univ
dc.description.affiliation Univ Tubingen, Med Res Ctr, Sect Transplantat Immunol & Immunohematol, D-72072 Tubingen, Germany
dc.description.affiliation Univ Tubingen, Ctr Regenerat Med, D-72072 Tubingen, Germany
dc.description.affiliation Univ Tubingen, Med Res Ctr, Dept Orthoped Surg, D-72072 Tubingen, Germany
dc.description.affiliation Univ Tubingen, Med & Nat Sci Res Ctr, D-72072 Tubingen, Germany
dc.description.affiliation Univ Tubingen, Inst Cell Biol, Dept Immunol, D-72072 Tubingen, Germany
dc.description.affiliation Universidade Federal de São Paulo, Dept Biophys, Escola Paulista Med, São Paulo, Brazil
dc.description.affiliation Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Biophys, Escola Paulista Med, São Paulo, Brazil
dc.description.sponsorshipID Landesstiftung Baden-Wurttemberg gGmbH (Stuttgart, Germany): P-LS-AS/HSPA8-13
dc.description.sponsorshipID Deutsche Forschungsgemeinschaft: GK794
dc.description.sponsorshipID NIH Roadmaps National Technology Centers for Networks and Pathways: U54 RR020843
dc.description.sponsorshipID NIH Roadmaps National Technology Centers for Networks and Pathways: R01 EB 005011
dc.identifier.file WOS000281933200005.pdf
dc.identifier.doi 10.3324/haematol.2009.018671
dc.description.source Web of Science
dc.identifier.wos WOS:000281933200005



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