Please use this identifier to cite or link to this item: https://doi.org/10.15480/882.3050
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dc.contributor.authorGrünherz, Lisanne-
dc.contributor.authorPrein, Carina-
dc.contributor.authorWinkler, Thomas-
dc.contributor.authorKirsch, Manuela-
dc.contributor.authorHopfner, Ursula-
dc.contributor.authorStreichert, Thomas-
dc.contributor.authorClausen-Schaumann, Hauke-
dc.contributor.authorZustin, Jozef-
dc.contributor.authorKirchhof, Kristin-
dc.contributor.authorMorlock, Michael M.-
dc.contributor.authorMachens, Hans-Günther-
dc.contributor.authorSchilling, Arndt Friedrich-
dc.date.accessioned2020-11-10T08:25:54Z-
dc.date.available2020-11-10T08:25:54Z-
dc.date.issued2020-04-13-
dc.identifier.citationJournal of Cellular and Molecular Medicine 10 (24): 5665-5674 (2020)de_DE
dc.identifier.issn1582-4934de_DE
dc.identifier.urihttp://hdl.handle.net/11420/7767-
dc.description.abstractIn patients with osteomalacia, a defect in bone mineralization leads to changed characteristics of the bone surface. Considering that the properties of the surrounding matrix influence function and differentiation of cells, we aimed to investigate the effect of osteoidosis on differentiation and function of osteoclasts. Based on osteomalacic bone biopsies, a model for osteoidosis in vitro (OIV) was established. Peripheral blood mononuclear cells were differentiated to osteoclasts on mineralized surfaces (MS) as internal control and on OIV. We observed a significantly reduced number of osteoclasts and surface resorption on OIV. Atomic force microscopy revealed a significant effect of the altered degree of mineralization on surface mechanics and an unmasking of collagen fibres on the surface. Indeed, coating of MS with RGD peptides mimicked the resorption phenotype observed in OIV, suggesting that the altered differentiation of osteoclasts on OIV might be associated with an interaction of the cells with amino acid sequences of unmasked extracellular matrix proteins containing RGD sequences. Transcriptome analysis uncovered a strong significant up-regulation of transmembrane glycoprotein TROP2 in osteoclastic cultures on OIV. TROP2 expression on OIV was also confirmed on the protein level and found on the bone surface of patients with osteomalacia. Taken together, our results show a direct influence of the mineralization state of the extracellular matrix surface on differentiation and function of osteoclasts on this surface which may be important for the pathophysiology of osteomalacia and other bone disorders with changed ratio of osteoid to bone.en
dc.language.isoende_DE
dc.publisherWiley-Blackwellde_DE
dc.relation.ispartofJournal of cellular and molecular medicinede_DE
dc.rightsCC BY 4.0de_DE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/de_DE
dc.subjectmechanotransductionde_DE
dc.subjectosteoclastde_DE
dc.subjectosteomalaciade_DE
dc.subjectRGD peptidede_DE
dc.subjectvitamin Dde_DE
dc.subject.ddc570: Biowissenschaften, Biologiede_DE
dc.titleOsteoidosis leads to altered differentiation and function of osteoclastsde_DE
dc.typeArticlede_DE
dc.identifier.doi10.15480/882.3050-
dc.type.diniarticle-
dcterms.DCMITypeText-
tuhh.identifier.urnurn:nbn:de:gbv:830-882.0111832-
tuhh.oai.showtruede_DE
tuhh.abstract.englishIn patients with osteomalacia, a defect in bone mineralization leads to changed characteristics of the bone surface. Considering that the properties of the surrounding matrix influence function and differentiation of cells, we aimed to investigate the effect of osteoidosis on differentiation and function of osteoclasts. Based on osteomalacic bone biopsies, a model for osteoidosis in vitro (OIV) was established. Peripheral blood mononuclear cells were differentiated to osteoclasts on mineralized surfaces (MS) as internal control and on OIV. We observed a significantly reduced number of osteoclasts and surface resorption on OIV. Atomic force microscopy revealed a significant effect of the altered degree of mineralization on surface mechanics and an unmasking of collagen fibres on the surface. Indeed, coating of MS with RGD peptides mimicked the resorption phenotype observed in OIV, suggesting that the altered differentiation of osteoclasts on OIV might be associated with an interaction of the cells with amino acid sequences of unmasked extracellular matrix proteins containing RGD sequences. Transcriptome analysis uncovered a strong significant up-regulation of transmembrane glycoprotein TROP2 in osteoclastic cultures on OIV. TROP2 expression on OIV was also confirmed on the protein level and found on the bone surface of patients with osteomalacia. Taken together, our results show a direct influence of the mineralization state of the extracellular matrix surface on differentiation and function of osteoclasts on this surface which may be important for the pathophysiology of osteomalacia and other bone disorders with changed ratio of osteoid to bone.de_DE
tuhh.publisher.doi10.1111/jcmm.15227-
tuhh.publication.instituteBiomechanik M-3de_DE
tuhh.identifier.doi10.15480/882.3050-
tuhh.type.opus(wissenschaftlicher) Artikel-
dc.type.driverarticle-
dc.type.casraiJournal Article-
tuhh.container.issue10de_DE
tuhh.container.volume24de_DE
tuhh.container.startpage5665de_DE
tuhh.container.endpage5674de_DE
dc.identifier.pmid32283567de_DE
dc.rights.nationallicensefalsede_DE
dc.identifier.scopus2-s2.0-85083310361de_DE
local.status.inpressfalsede_DE
local.type.versionsubmittedVersionde_DE
item.grantfulltextopen-
item.openairetypeArticle-
item.fulltextWith Fulltext-
item.languageiso639-1en-
item.creatorOrcidGrünherz, Lisanne-
item.creatorOrcidPrein, Carina-
item.creatorOrcidWinkler, Thomas-
item.creatorOrcidKirsch, Manuela-
item.creatorOrcidHopfner, Ursula-
item.creatorOrcidStreichert, Thomas-
item.creatorOrcidClausen-Schaumann, Hauke-
item.creatorOrcidZustin, Jozef-
item.creatorOrcidKirchhof, Kristin-
item.creatorOrcidMorlock, Michael M.-
item.creatorOrcidMachens, Hans-Günther-
item.creatorOrcidSchilling, Arndt Friedrich-
item.cerifentitytypePublications-
item.creatorGNDGrünherz, Lisanne-
item.creatorGNDPrein, Carina-
item.creatorGNDWinkler, Thomas-
item.creatorGNDKirsch, Manuela-
item.creatorGNDHopfner, Ursula-
item.creatorGNDStreichert, Thomas-
item.creatorGNDClausen-Schaumann, Hauke-
item.creatorGNDZustin, Jozef-
item.creatorGNDKirchhof, Kristin-
item.creatorGNDMorlock, Michael M.-
item.creatorGNDMachens, Hans-Günther-
item.creatorGNDSchilling, Arndt Friedrich-
item.openairecristypehttp://purl.org/coar/resource_type/c_6501-
crisitem.author.deptBiomechanik M-3-
crisitem.author.deptBiomechanik M-3-
crisitem.author.deptBiomechanik M-3-
crisitem.author.orcid0000-0002-3559-106-
crisitem.author.orcid0000-0003-2524-6464-
crisitem.author.orcid0000-0002-6588-720X-
crisitem.author.orcid0000-0002-9413-0310-
crisitem.author.orcid0000-0002-5330-2454-
crisitem.author.orcid0000-0002-3852-6433-
crisitem.author.orcid0000-0001-7022-1069-
crisitem.author.parentorgStudiendekanat Maschinenbau-
crisitem.author.parentorgStudiendekanat Maschinenbau-
crisitem.author.parentorgStudiendekanat Maschinenbau-
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