Evaluation des Immunophilins FKBP51 als therapeutisches Ziel in der Therapie der Osteoarthrose
Evaluation of the immunophilin FKBP51 as therapeutic target in the therapy of osteoarthritis
von Ruben Sonnenbrodt
Datum der mündl. Prüfung:2023-05-02
Erschienen:2023-04-21
Betreuer:Prof. Dr. Nicolai Miosge
Gutachter:Prof. Dr Arndt Schilling
Gutachter:Prof. Dr. Thomas Meyer
Dateien
Name:2023_04_19_Evaluation des Immunophilins FKBP...pdf
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Format:PDF
Zusammenfassung
Englisch
Osteoarthritis (OA) is a degenerative disease leading to a destruction of the articular cartilage and the surrounding tissues of the affected joints. In the late stages it cumulates in a complete loss of joint function. New regenerative therapy concepts involving stem cells are emerging, promising a regeneration of the articular cartilage, but regneration of the diseased cartilage tends to be a great challenge due to limited intrinsic repair capacity. Chondrogenic progenitor cells (CPC) found in the articular cartilage in the late stages of OA show a regenerative potential that might be stimulated by drug therapy. Purpose of this experimental study was to investigate the role of the immunophilin FK506-binding protein 51 (FKBP51) in CPCs in order to evaluate its role as a potential pharmacological target. FKBP51 is a protein with many different functions, and known as an modulator of the NF-κB pathway, which might play a role in the progression OA. To investigate the function of the protein in CPCs I used the CRISPR/Cas-9 method with the aim to create a FKBP51 knockout and RNA-silencing with small interfering-RNAs. The results detected FKBP51 in CPCs for the first time on the level of mRNA and protein. The knockdown and knockout experiments showed results with different possibilities of interpretation. The results provide the foundation of further investigations to understand the importance of FKBP51 in CPCs.
Keywords: FKBP51; osteoarthritis; chondrogenic progenitor cells; CRISPR/Cas