| dc.contributor.advisor | Miosge, Nicolai Prof. Dr. | |
| dc.contributor.author | Haßfeld, Jochen | |
| dc.date.accessioned | 2020-06-19T07:35:28Z | |
| dc.date.available | 2020-07-06T22:50:03Z | |
| dc.date.issued | 2020-06-19 | |
| dc.identifier.uri | http://hdl.handle.net/21.11130/00-1735-0000-0005-13E4-4 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-8049 | |
| dc.language.iso | deu | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject.ddc | 610 | de |
| dc.title | Der Einfluss von YWHAE auf das chondrogene Potenzial von chondrogenen Progenitorzellen | de |
| dc.type | doctoralThesis | de |
| dc.title.translated | Influence of YWHAE on the Chondrogenic Potential of Chondrogenic Progenitor Cells | de |
| dc.contributor.referee | Schilling, Arndt Prof. Dr. | |
| dc.date.examination | 2020-06-29 | |
| dc.description.abstracteng | The goal of this thesis was to investigate the influence of YWHAE on the chondrogenic potential of chondrogenic progenitor cells (CPC). If it would be possible to enhance their chondrogenic potential, CPCs would be a possible option as cell therapy to treat osteoarthritis. First, we tried to generate a homozygous YWHAE knockout in CPCs by using the CRISPR/Cas9 method. Due to not definitely known processes, possibly regulation in the CPCs or apoptosis, no CPCs with a homozygous knockout could be cultivated. It was possible however to generate a heterozygous YWHAE Knockout in CPCs, which leads to reduction of the YWHAE protein level to about 25 %. If these manipulated CPCs are cultivated in alginate culture, they produce significantly more SOX9 and less RUN2 than not manipulated CPCs. This leads to the conclusion that YWHAE has a negative impact on the synthesis of the chondrogenic factor SOX9 and a positive impact on the synthesis of the factor RUNX2. Despite this promising impact on the regulation factors CPCs with a heterozygous YWHAE knockout do not produce an increasing number of COL2. There was no reduction of the osteogenic factor COL1. The ACAN-mRNA level, tested by qPCR, does show a significantly reduction, which is also not a promising result. Furthermore, histologic images of alginate cultures do not show visible changes of the chondrogenic markers. It seems that a direct reduction of YWHAE is not a promising option to enhance the chondrogenic potential of CPCs.
Further investigations are necessary to determine the additional effects of YWHAE on CPCs, which could influence the ECM synthesis. The exact interaction between SOX9, RUNX2 and YWHAE should be the goal of new studies. With more knowledge it could be possible to block the connection between YWHAE and these two factors exclusively and not to manipulate the other effects YWHAE has on CPCs. Another important field of investigation could be to the interaction between the regulators SOX9 and RUNX2 with COL2 to find out why no influence has been detected. If it would be possible to enhance the chondrogenic potential of CPCs by manipulation of YWHAE or another factor, more studies besides measuring of chondrogenic markers would be necessary to determine the possible use of manipulated CPCs as a therapeutic option. | de |
| dc.contributor.coReferee | Mausberg, Rainer Prof. Dr. | |
| dc.subject.eng | YWHAE | de |
| dc.subject.eng | CPC | de |
| dc.subject.eng | Chondrogenic Progenitor Cells | de |
| dc.subject.eng | Osteoarthritis | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-21.11130/00-1735-0000-0005-13E4-4-1 | |
| dc.affiliation.institute | Medizinische Fakultät | de |
| dc.subject.gokfull | Medizin (PPN619874732) | de |
| dc.subject.gokfull | Zahn-, Mund- und Kieferheilkunde - Allgemein- und Gesamtdarstellungen (PPN619876360) | de |
| dc.description.embargoed | 2020-07-06 | |
| dc.identifier.ppn | 1701160587 | |