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.authorStaudt, Nicole D.
dc.contributor.authorAicher, Wilhelm K.
dc.contributor.authorKalbacher, Hubert
dc.contributor.authorStevanovic, Stefan
dc.contributor.authorCarmona, Adriana Karaoglanovic [UNIFESP]
dc.contributor.authorBogyo, Matthew
dc.contributor.authorKlein, Gerd
dc.contributor.institutionUniv Tubingen
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionStanford Univ
dc.date.accessioned2016-01-24T14:05:24Z
dc.date.available2016-01-24T14:05:24Z
dc.date.issued2010-09-01
dc.description.abstractBackground 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.affiliationUniv Tubingen, Med Res Ctr, Sect Transplantat Immunol & Immunohematol, D-72072 Tubingen, Germany
dc.description.affiliationUniv Tubingen, Ctr Regenerat Med, D-72072 Tubingen, Germany
dc.description.affiliationUniv Tubingen, Med Res Ctr, Dept Orthoped Surg, D-72072 Tubingen, Germany
dc.description.affiliationUniv Tubingen, Med & Nat Sci Res Ctr, D-72072 Tubingen, Germany
dc.description.affiliationUniv Tubingen, Inst Cell Biol, Dept Immunol, D-72072 Tubingen, Germany
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biophys, Escola Paulista Med, São Paulo, Brazil
dc.description.affiliationStanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biophys, Escola Paulista Med, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipLandesstiftung Baden-Wurttemberg gGmbH (Stuttgart, Germany)
dc.description.sponsorshipDeutsche Forschungsgemeinschaft
dc.description.sponsorshipNIH Roadmaps National Technology Centers for Networks and Pathways
dc.description.sponsorshipIDLandesstiftung Baden-Wurttemberg gGmbH (Stuttgart, Germany): P-LS-AS/HSPA8-13
dc.description.sponsorshipIDDeutsche Forschungsgemeinschaft: GK794
dc.description.sponsorshipIDNIH Roadmaps National Technology Centers for Networks and Pathways: U54 RR020843
dc.description.sponsorshipIDNIH Roadmaps National Technology Centers for Networks and Pathways: R01 EB 005011
dc.format.extent1452-1460
dc.identifierhttp://dx.doi.org/10.3324/haematol.2009.018671
dc.identifier.citationHaematologica-the Hematology Journal. Pavia: Ferrata Storti Foundation, v. 95, n. 9, p. 1452-1460, 2010.
dc.identifier.doi10.3324/haematol.2009.018671
dc.identifier.fileWOS000281933200005.pdf
dc.identifier.issn0390-6078
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/32856
dc.identifier.wosWOS:000281933200005
dc.language.isoeng
dc.publisherFerrata Storti Foundation
dc.relation.ispartofHaematologica-the Hematology Journal
dc.rightsAcesso aberto
dc.subjectstem cell nicheen
dc.subjectproteolytic microenvironmenten
dc.subjectproteasesen
dc.subjectcell adhesionen
dc.subjectcysteine cathepsinsen
dc.subjectactive site labelingen
dc.titleCathepsin X is secreted by human osteoblasts, digests CXCL-12 and impairs adhesion of hematopoietic stem and progenitor cells to osteoblastsen
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