Navigation/Menü: Links auf weitere Seiten dieser Website
Objekt-Metadaten
| Interaktionen von Myelomzellen mit Osteoklasten und Osteoblasten und Einfluss von Proteasominhibitoren auf den Knochenstoffwechsel bei Patienten mit multiplem Myelom Heider, Ulrike |
| Main title | Interaktionen von Myelomzellen mit Osteoklasten und Osteoblasten und Einfluss von Proteasominhibitoren auf den Knochenstoffwechsel bei Patienten mit multiplem Myelom |
| Title variations | Interactions of myeloma cells with osteoclasts and osteoblasts and influence of proteasome inhibitors on myeloma bone disease |
| Author(s) | Heider, Ulrike
Place of birth: Rostock |
| 1. Referee | Prof. Dr. med. Hermann Einsele |
| Further Referee(s) | Prof. Dr. med. Hartmut Goldschmidt |
| Keywords | multiple myeloma; lytic bone lesions; osteoclast; osteoblast; RANKL; DKK-1; proteasome inhibitor; bortezomib |
| Classification (DDC) | 610 Medical sciences; Medicine |
| Summary | Interactions between myeloma cells and cells of the bone marrow microenvironment lead to osteoclast activation and osteoblast inhibition (uncoupling), resulting in lytic bone lesions. We could show that myeloma cells express RANKL, a potent stimulator of osteoclast activity, and that the expression of RANKL correlates with osteolytic bone disease. In addition, myeloma cells induce RANKL expression by stromal cells and lead to degradation and reduced expression of the RANKL antagonist OPG. Furthermore, we could show that myeloma cells produce DKK-1, an inhibitor of Wnt/ ß catenin signalling pathway, which is crucial for osteoblast differentiation, and that serum DKK-1 is elevated in myeloma patients and correlates with the extend of bone disease. In return, cells of the bone marrow microenvironment stimulate proliferation, survival, migration and invasion of myeloma cells. Based on these findings, novel therapies have been developed targeting myeloma bone disease, as denosumab, a recombinant antibody against RANKL, or an anti-DKK-1- antibody. The proteasome inhibitor bortezomib is another drug that could influence bone metabolism in myeloma patients. We could show that bortezomib on one hand inhibits osteoclast differentiation and activity, and on the other hand stimulates osteoblast differentiation. With the identification of these new pathomechnisms, novel targets for the treatment of myeloma bone disease could be defined. |
| Documents |
PDF-Datei von FUDISS_thesis_000000022124
If your browser can't open the file, please download the file first and then open it
|
| FU Department | Department of Medicine - Charité - University Medicine Berlin |
| Year of publication | 2011 |
| Document type | Habilitation treatise |
| Media type/Format | Text |
| Language | German |
| Terms of use/Rights | Nutzungsbedingungen |
| Date of defense | 2011-02-14 |
| Created at | 2011-03-31 : 12:17:56 |
| Last changed | 2011-03-31 : 12:22:06 |
| Static URL | http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000022124 |
| NBN | urn:nbn:de:kobv:188-fudissthesis000000022124-4 |
| Statistics | |
| E-mail address | ulrike.heider@charite.de |
