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dc.date.accessioned2018-08-25T11:09:08Z
dc.date.available2018-08-25T11:09:08Z
dc.date.created2017-02-06T08:56:43Z
dc.date.issued2017
dc.identifier.citationJafari, Abbas Qanie, Diyako Andersen, Thomas L. Zhang, Yuxi Chen, Li Postert, Benno Parsons, Stuart Ditzel, Nicholas Khosla, Sundeep Johansen, Harald Thidemann Kjærsgaard-Andersen, Per Delaissé, Jean-Marie Abdallah, Basem M. Hesselson, Daniel Solberg, Rigmor Kassem, Moustapha . Legumain regulates differentiation fate of human bone marrow stromal cells and is altered in postmenopausal osteoporosis. Stem Cell Reports. 2017, 8(2), 373-386
dc.identifier.urihttp://hdl.handle.net/10852/63761
dc.description.abstractSecreted factors are a key component of stem cell niche and their dysregulation compromises stem cell function. Legumain is a secreted cysteine protease involved in diverse biological processes. Here, we demonstrate that legumain regulates lineage commitment of human bone marrow stromal cells and that its expression level and cellular localization are altered in postmenopausal osteoporotic patients. As shown by genetic and pharmacological manipulation, legumain inhibited osteoblast (OB) differentiation and in vivo bone formation through degradation of the bone matrix protein fibronectin. In addition, genetic ablation or pharmacological inhibition of legumain activity led to precocious OB differentiation and increased vertebral mineralization in zebrafish. Finally, we show that localized increased expression of legumain in bone marrow adipocytes was inversely correlated with adjacent trabecular bone mass in a cohort of patients with postmenopausal osteoporosis. Our data suggest that altered proteolytic activity of legumain in the bone microenvironment contributes to decreased bone mass in postmenopausal osteoporosis.en_US
dc.languageEN
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleLegumain regulates differentiation fate of human bone marrow stromal cells and is altered in postmenopausal osteoporosisen_US
dc.typeJournal articleen_US
dc.creator.authorJafari, Abbas
dc.creator.authorQanie, Diyako
dc.creator.authorAndersen, Thomas L.
dc.creator.authorZhang, Yuxi
dc.creator.authorChen, Li
dc.creator.authorPostert, Benno
dc.creator.authorParsons, Stuart
dc.creator.authorDitzel, Nicholas
dc.creator.authorKhosla, Sundeep
dc.creator.authorJohansen, Harald Thidemann
dc.creator.authorKjærsgaard-Andersen, Per
dc.creator.authorDelaissé, Jean-Marie
dc.creator.authorAbdallah, Basem M.
dc.creator.authorHesselson, Daniel
dc.creator.authorSolberg, Rigmor
dc.creator.authorKassem, Moustapha
cristin.unitcode185,15,23,30
cristin.unitnameFarmasøytisk biovitenskap
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.cristin1447190
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Stem Cell Reports&rft.volume=8&rft.spage=373&rft.date=2017
dc.identifier.jtitleStem Cell Reports
dc.identifier.volume8
dc.identifier.issue2
dc.identifier.startpage373
dc.identifier.endpage386
dc.identifier.doihttp://dx.doi.org/10.1016/j.stemcr.2017.01.003
dc.identifier.urnURN:NBN:no-66313
dc.type.documentTidsskriftartikkelen_US
dc.type.peerreviewedPeer reviewed
dc.source.issn2213-6711
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/63761/2/40%2529JafariA_OsteoblastDiff_Osteoporosis_StemCellRep_2017.pdf
dc.type.versionPublishedVersion


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