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dc.date.accessioned2020-10-28T10:07:01Z
dc.date.available2020-10-28T10:07:01Z
dc.date.issued2020
dc.identifier.urihttp://hdl.handle.net/10852/80762
dc.description.abstractLegumain is an enzyme present in most cells but its dysregulation is associated with several diseases. During stem cell differentiation, legumain stimulates fat cell and inhibits osteoblast differentiation. This thesis sheds new light on regulation and function of legumain and explores the possibility of using known drugs to target legumain. Legumain is normally present in acidic organelles but can be found outside the cell. This dissertation summarizes extracellular roles of legumain and describes its presence in bone cell exosomes. Lansoprazole is a commonly used drug against excessive stomach acid production. It was shown that this drug directly inhibits legumain, which could explain osteoporosis as a side effect associated with chronic lansoprazole use. Vitamin D is important for the development of healthy bones and it was found that this vitamin upregulated legumain activity in the early stages of osteoblast differentiation. Furthermore, this thesis shows that legumain downregulates expression of vitamin D receptor and enhances expression and degradation of fibronectin. Dysregulation of vitamin D and fibronectin is associated with progression of various pathological conditions.en_US
dc.language.isoenen_US
dc.relation.haspartPaper I: Lunde NN, Bosnjak T, Solberg R, Johansen HT. Mammalian legumain - A lysosomal cysteine protease with extracellular functions? Biochimie, 166, 77-83; 2019. DOI: 10.1016/j.biochi.2019.06.002. The article is included in the thesis. Also available at: https://doi.org/10.1016/j.biochi.2019.06.002
dc.relation.haspartPaper II: Bosnjak T, Solberg R, Hemati PD, Jafari A, Kassem M, Johansen HT. Lansoprazole inhibits the cysteine protease legumain by binding to the active site. Basic & Clinical Pharmacology & Toxicology, 125 (2), 89-99; 2019. DOI: 10.1111/bcpt.13230. The article is not available in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1111/bcpt.13230
dc.relation.haspartPaper III: Bosnjak T, Solberg R, Arnekleiv GL, Jafari A, Hesselson D, Bassatne A, Fuleihan GEH, Kassem M and Johansen HT. Regulatory effects of vitamin D3 on the cysteine protease legumain: Relevance to bone biology. Submitted. To be published. The paper is not available in DUO awaiting publishing.
dc.relation.haspartPaper IV: Bosnjak T, Solberg R, Jafari A, Poreba M, Hesselson D, Haug KBF, Øvstebø R., Drag M, Kassem M, Johansen HT, Lunde NN. Legumain enhances fibronectin production and both proteins are present in bone cell exosomes. Manuscript. To be published. The paper is not available in DUO awaiting publishing.
dc.relation.urihttps://doi.org/10.1016/j.biochi.2019.06.002
dc.relation.urihttps://doi.org/10.1111/bcpt.13230
dc.titleRegulation and functional studies of the cysteine protease legumain in bone cell biologyen_US
dc.typeDoctoral thesisen_US
dc.creator.authorBosnjak, Tatjana
dc.identifier.urnURN:NBN:no-83850
dc.type.documentDoktoravhandlingen_US
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/80762/1/PhD-Bosnjak-2020.pdf


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