TY - JOUR A1 - Ziouti, Fani A1 - Rummler, Maximilian A1 - Steyn, Beatrice A1 - Thiele, Tobias A1 - Seliger, Anne A1 - Duda, Georg N. A1 - Bogen, Bjarne A1 - Willie, Bettina M. A1 - Jundt, Franziska T1 - Prevention of bone destruction by mechanical loading is not enhanced by the Bruton's tyrosine kinase inhibitor CC-292 in myeloma bone disease JF - International Journal of Molecular Sciences N2 - Limiting bone resorption and regenerating bone tissue are treatment goals in myeloma bone disease (MMBD). Physical stimuli such as mechanical loading prevent bone destruction and enhance bone mass in the MOPC315.BM.Luc model of MMBD. It is unknown whether treatment with the Bruton's tyrosine kinase inhibitor CC-292 (spebrutinib), which regulates osteoclast differentiation and function, augments the anabolic effect of mechanical loading. CC-292 was administered alone and in combination with axial compressive tibial loading in the MOPC315.BM.Luc model for three weeks. However, neither CC-292 alone nor its use in combination with mechanical loading was more effective in reducing osteolytic bone disease or rescuing bone mass than mechanical stimuli alone, as evidenced by microcomputed tomography (microCT) and histomorphometric analysis. Further studies are needed to investigate novel anti-myeloma and anti-resorptive strategies in combination with physical stimuli to improve treatment of MMBD. KW - multiple myeloma KW - cancer-induced bone disease KW - Bruton's tyrosine kinase inhibitor CC-292 KW - skeletal mechanobiology KW - bone adaptation KW - mechanical loading Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284943 SN - 1422-0067 VL - 22 IS - 8 ER - TY - JOUR A1 - Herrmann, Marietta A1 - Engelke, Klaus A1 - Ebert, Regina A1 - Müller-Deubert, Sigrid A1 - Rudert, Maximilian A1 - Ziouti, Fani A1 - Jundt, Franziska A1 - Felsenberg, Dieter A1 - Jakob, Franz T1 - Interactions between muscle and bone — Where physics meets biology JF - Biomolecules N2 - Muscle and bone interact via physical forces and secreted osteokines and myokines. Physical forces are generated through gravity, locomotion, exercise, and external devices. Cells sense mechanical strain via adhesion molecules and translate it into biochemical responses, modulating the basic mechanisms of cellular biology such as lineage commitment, tissue formation, and maturation. This may result in the initiation of bone formation, muscle hypertrophy, and the enhanced production of extracellular matrix constituents, adhesion molecules, and cytoskeletal elements. Bone and muscle mass, resistance to strain, and the stiffness of matrix, cells, and tissues are enhanced, influencing fracture resistance and muscle power. This propagates a dynamic and continuous reciprocity of physicochemical interaction. Secreted growth and differentiation factors are important effectors of mutual interaction. The acute effects of exercise induce the secretion of exosomes with cargo molecules that are capable of mediating the endocrine effects between muscle, bone, and the organism. Long-term changes induce adaptations of the respective tissue secretome that maintain adequate homeostatic conditions. Lessons from unloading, microgravity, and disuse teach us that gratuitous tissue is removed or reorganized while immobility and inflammation trigger muscle and bone marrow fatty infiltration and propagate degenerative diseases such as sarcopenia and osteoporosis. Ongoing research will certainly find new therapeutic targets for prevention and treatment. KW - muscle KW - bone KW - mechanosensing KW - mechanotransduction KW - myokines KW - osteokines adaptation Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-203399 SN - 2218-273X VL - 10 IS - 3 ER - TY - JOUR A1 - Maichl, Daniela Simone A1 - Kirner, Julius Arthur A1 - Beck, Susanne A1 - Cheng, Wen-Hui A1 - Krug, Melanie A1 - Kuric, Martin A1 - Ade, Carsten Patrick A1 - Bischler, Thorsten A1 - Jakob, Franz A1 - Hose, Dirk A1 - Seckinger, Anja A1 - Ebert, Regina A1 - Jundt, Franziska T1 - Identification of NOTCH-driven matrisome-associated genes as prognostic indicators of multiple myeloma patient survival JF - Blood Cancer Journal N2 - No abstract available. KW - cancer microenvironment KW - myeloma Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357598 VL - 13 ER - TY - JOUR A1 - Wong, David A1 - Winter, Oliver A1 - Hartig, Christina A1 - Siebels, Svenja A1 - Szyska, Martin A1 - Tiburzy, Benjamin A1 - Meng, Lingzhang A1 - Kulkarni, Upasana A1 - Fähnrich, Anke A1 - Bommert, Kurt A1 - Bargou, Ralf A1 - Berek, Claudia A1 - Van, Trung Chu A1 - Bogen, Bjarne A1 - Jundt, Franziska A1 - Manz, Rudolf Armin T1 - Eosinophils and Megakaryocytes Support the Early Growth of Murine MOPC315 Myeloma Cells in Their Bone Marrow Niches JF - PLOS ONE N2 - Multiple myeloma is a bone marrow plasma cell tumor which is supported by the external growth factors APRIL and IL-6, among others. Recently, we identified eosinophils and megakaryocytes to be functional components of the micro-environmental niches of benign bone marrow plasma cells and to be important local sources of these cytokines. Here, we investigated whether eosinophils and megakaryocytes also support the growth of tumor plasma cells in the MOPC315. BM model for multiple myeloma. As it was shown for benign plasma cells and multiple myeloma cells, IL-6 and APRIL also supported MOPC315. BM cell growth in vitro, IL-5 had no effect. Depletion of eosinophils in vivo by IL-5 blockade led to a reduction of the early myeloma load. Consistent with this, myeloma growth in early stages was retarded in eosinophil-deficient Delta dblGATA-1 mice. Late myeloma stages were unaffected, possibly due to megakaryocytes compensating for the loss of eosinophils, since megakaryocytes were found to be in contact with myeloma cells in vivo and supported myeloma growth in vitro. We conclude that eosinophils and megakaryocytes in the niches for benign bone marrow plasma cells support the growth of malignant plasma cells. Further investigations are required to test whether perturbation of these niches represents a potential strategy for the treatment of multiple myeloma. KW - plasma cells KW - human multiple-myeloma KW - immune response KW - receptor expression KW - B-cells KW - stromal cells KW - dexamethasone KW - april KW - survival KW - Interleukin-5 Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115269 VL - 9 IS - 10 ER - TY - JOUR A1 - Hofgaard, Peter O. A1 - Jodal, Henriette C. A1 - Bommert, Kurt A1 - Huard, Bertrand A1 - Caers, Jo A1 - Carlsen, Harald A1 - Schwarzer, Rolf A1 - Schünemann, Nicole A1 - Jundt, Franziska A1 - Lindeberg, Mona M. A1 - Bogen, Bjarne T1 - A Novel Mouse Model for Multiple Myeloma (MOPC315.BM) That Allows Noninvasive Spatiotemporal Detection of Osteolytic Disease JF - PLoS One N2 - Multiple myeloma (MM) is a lethal human cancer characterized by a clonal expansion of malignant plasma cells in bone marrow. Mouse models of human MM are technically challenging and do not always recapitulate human disease. Therefore, new mouse models for MM are needed. Mineral-oil induced plasmacytomas (MOPC) develop in the peritoneal cavity of oil-injected BALB/c mice. However, MOPC typically grow extramedullary and are considered poor models of human MM. Here we describe an in vivo-selected MOPC315 variant, called MOPC315.BM, which can be maintained in vitro. When injected i.v. into BALB/c mice, MOPC315.BM cells exhibit tropism for bone marrow. As few as 10\(^4\) MOPC315.BM cells injected i.v. induced paraplegia, a sign of spinal cord compression, in all mice within 3-4 weeks. MOPC315.BM cells were stably transfected with either firefly luciferase (MOPC315.BM.Luc) or DsRed (MOPC315.BM.DsRed) for studies using noninvasive imaging. MOPC315.BM.Luc cells were detected in the tibiofemoral region already 1 hour after i.v. injection. Bone foci developed progressively, and as of day 5, MM cells were detected in multiple sites in the axial skeleton. Additionally, the spleen (a hematopoietic organ in the mouse) was invariably affected. Luminescent signals correlated with serum myeloma protein concentration, allowing for easy tracking of tumor load with noninvasive imaging. Affected mice developed osteolytic lesions. The MOPC315.BM model employs a common strain of immunocompetent mice (BALB/c) and replicates many characteristics of human MM. The model should be suitable for studies of bone marrow tropism, development of osteolytic lesions, drug testing, and immunotherapy in MM. KW - resistance KW - CD4(+) T-cells KW - tumor specific antigen KW - plasma cells KW - B cell KW - C57BL/KALWRIJ mouse KW - bone disease KW - scid mice KW - idiotype KW - differentiation Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131117 VL - 7 IS - 12 ER -