Refine
Has Fulltext
- yes (19)
Is part of the Bibliography
- yes (19)
Year of publication
Document Type
- Journal article (19)
Language
- English (19) (remove)
Keywords
- B cells (2)
- BMP (2)
- BMP-2 (2)
- Bone morphogenetic protein-2 (2)
- bone regeneration (2)
- gene expression (2)
- growth factor beta (2)
- multiple myeloma (2)
- subcutaneous animal model (2)
- tissue engineering (2)
Institute
- Lehrstuhl für Tissue Engineering und Regenerative Medizin (19)
- Julius-von-Sachs-Institut für Biowissenschaften (6)
- Theodor-Boveri-Institut für Biowissenschaften (4)
- Abteilung für Molekulare Innere Medizin (in der Medizinischen Klinik und Poliklinik II) (3)
- Klinik und Poliklinik für Mund-, Kiefer- und Plastische Gesichtschirurgie (3)
- Institut für Funktionsmaterialien und Biofabrikation (2)
- Institut für Organische Chemie (2)
- Abteilung für Funktionswerkstoffe der Medizin und der Zahnheilkunde (1)
- Augenklinik und Poliklinik (1)
- Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie (Chirurgische Klinik I) (1)
Sonstige beteiligte Institutionen
EU-Project number / Contract (GA) number
- 607051 (3)
- 242175-VascuBone (1)
- 242175‐VascuBone (1)
- 309962 (1)
- 723770 (1)
Multiple myeloma (MM) represents a haematological cancer characterized by the pathological hyper proliferation of antibody-producing B-lymphocytes. Patients typically suffer from kidney malfunction and skeletal disorders. In the context of MM, the transforming growth factor β (TGFβ) member Activin A was recently identified as a promoter of both accompanying symptoms. Because studies have shown that bone morphogenetic protein (BMP)-2-mediated activities are counteracted by Activin A, we analysed whether BMP2, which also binds to the Activin A receptors ActRII and ActRIIB but activates the alternative SMAD-1/5/8 pathway, can be used to antagonize Activin A activities, such as in the context of MM. Therefore three BMP2 derivatives were generated with modified binding activities for the type II (ActRIIB) and/or type I receptor (BMPRIA) showing either increased or decreased BMP2 activity. In the context of MM these BMP2 muteins show two functionalities since they act as a) an anti-proliferative/apoptotic agent against neoplastic B-cells, b) as a bone-formation promoting growth factor. The molecular basis of both activities was shown in two different cellular models to clearly rely on the properties of the investigated BMP2 muteins to compete for the binding of Activin A to the Activin type II receptors. The experimental outcome suggests new therapeutic strategies using BMP2 variants in the treatment of MM-related pathologies.