Nachweis und isoformspezifische Funktion von HMGB1-Protein im osteoarthritischen Knorpel und chondrogenen Progenitorzellen

Lehmann, Christoph

dc.contributor.advisor	Miosge, Nicolai Prof. Dr.
dc.contributor.author	Lehmann, Christoph
dc.date.accessioned	2020-07-06T14:28:45Z
dc.date.available	2020-07-07T22:50:02Z
dc.date.issued	2020-07-06
dc.identifier.uri	http://hdl.handle.net/21.11130/00-1735-0000-0005-1404-0
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-8057
dc.language.iso	deu	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc	610	de
dc.title	Nachweis und isoformspezifische Funktion von HMGB1-Protein im osteoarthritischen Knorpel und chondrogenen Progenitorzellen	de
dc.type	doctoralThesis	de
dc.title.translated	Detection and isoform-specific function of high mobility group box protein 1 (HMGB1) in human osteoarthritic cartilage and chondrogenic progenitor cells.	de
dc.contributor.referee	Mausberg, Rainer Prof. Dr.
dc.date.examination	2020-06-29
dc.description.abstracteng	Osteoarthritis (OA) is a common musculoskeletal disease in the elderly, characterized by painful aseptic inflammation, destruction of the joint surface and subchondral sclerosis. In late-stage OA, human articular cartilage harbors a unique progenitor cell population (CPCs) with stem cell characteristics such as multipotency and migratory activity. The aim of the present study was to analyze the HMGB1 distribution in OA cartilage and its effect on CPCs. HMGB1 protein is expressed by all eukaryotic cells and it is named for its rapid mobility on electrophoresis gels. HMGB1 was originally identified as a DNA binding protein. Extracellular HMGB1 play significantly different roles in inflammation, injury and infection response and cell migration depending on post-translational modifications. Oxidized HMGB1 (also called disulfide HMGB1) is a pro-inflammatory cytokine, whereas by contrast reduced HMGB1 (fully-reduced HMGB1) activates cell migration. The immunohistochemical study demonstrated that the HMGB1 protein level is increased in deep layers of OA cartilage. Breaks in tidemark packed with blood vessels that had vascularized into the cartilage tissue stained HMGB1 positive in IHC. Immuncytochemistry (ICC) identified HMGB1 in chondrocyte nuclear and cytoplasm. In CPCs, the signal was limited to the nuclear region. Western blot analysis for HMGB1 indicated a high level of HMGB1 protein in OA chondrocytes, whereas healthy chondrocytes and CPCs shown a lower HMGB1 protein expression. ICC also identified extracellular receptors such as RAGE (Receptor for Advanced Glycation Endproducts) and TLR4 (Toll-like receptor 4) on the CPC membrane. CPC migration assay identified fully-reduced HMGB1 as a pro-migratory cytokine. CPC stimulation with disulfide HMGB1 did not enhance the expression of pro-inflammatory cytokines such as IL6 and TNFα.	de
dc.contributor.coReferee	Schilling, Arndt Prof. Dr.
dc.subject.eng	Osteoarthritis	de
dc.subject.eng	HMGB1	de
dc.subject.eng	Chondrogenic Progenior Cells	de
dc.identifier.urn	urn:nbn:de:gbv:7-21.11130/00-1735-0000-0005-1404-0-5
dc.affiliation.institute	Medizinische Fakultät	de
dc.subject.gokfull	GOK-MEDIZIN	de
dc.description.embargoed	2020-07-07
dc.identifier.ppn	1703803191 1703803175 1703803159 1703803132

Dateien

Name:Dissertation Christoph Lehmann.pdf

Größe:9.370Mb

Format:PDF

Öffnen

Name:: Dissertation Christoph Lehmann.pdf
Größe:: 9.370Mb
Format:: PDF

Öffnen

Das Dokument erscheint in:

Human- und Zahnmedizin [2870]

Zur Kurzanzeige