Research Blog & News
Two international experts providing insights into MSC epigenetics and iron metabolism
The Bone Lab thanks Laura Silvestri from the Università Vita-Salute San Raffaele in Milan, Italy and Alexander Rauch from the University of Southern Denmark for their fantastic talks on iron metabolism and the control of hepcidin expression and the epigenetic control of MSC differentiation into osteoblasts and adipocytes. We learned a lot and are looking forward to further collaborations!
How does diabetes impact bone health?
Diabetes mellitus is a widespread metabolic disease, with negative/adverse effects on many organ systems. Diabetes also significantly affects bone health. An increased risk of bone fractures and impaired fracture healing has been observed in patients, but the mechanisms are not fully understood. In order to investigate the links between diabetes and the bone system, the EU project “FIDELIO” will run for four years starting October 2019. This European Training Network, coordinated by scientists from the Faculty of Medicine of the Technical University of Dresden, is funded by the EU Marie Skłodowska-Curie Actions programme with a total of 3.8 million €. In FIDELIO, 14 ambitious and creative young scientists will be trained to tackle the future challenges of an ageing society.
To prevent bones from breaking, they must be healthy and strong. The regulation of bone metabolism is influenced by hormones, mechanical stress, and genetic factors. Diabetes mellitus is a serious and wide-spread condition affecting the whole body. Well-known complications include the heart, the kidneys or the eyes. However, what has only recently been discovered is that diabetes mellitus also has serious adverse effects on bone metabolism, resulting in an increased fracture risk and poor healing. How exactly do type 1 and type 2 diabetes damage the skeleton? What role do inflammatory processes and vascular damage play? Which new therapeutic approaches result from this? How can fractures be more effectively prevented? These are some of the questions that the scientists of the FIDELIO network aim to answer. Using a network of young talents and cooperation with industry, they expect to obtain novel insights into the risk factors and mechanisms of diabetic bone disease. New genetic and diagnostic markers could better identify patients at risk for bone fractures. Imaging techniques are essential for a more precise diagnosis. In collaboration with industry, new imaging-based methods for bone visualization will be developed to ultimately detect bone changes before they lead to fractures.
FIDELIO stands for “Training network for research into bone Fragility In Diabetes in Europe towards a personaLised medIcine apprOach” and is coordinated by the professors Martina Rauner and Lorenz Hofbauer of the Bone Lab of the Medical Faculty of the TU Dresden. “It will take highly qualified and specially trained scientists and clinicians to develop a new field of research into diabetes and bone. FIDELIO will educate 14 young scientists in an interdisciplinary, intersectoral and international environment and provide them with extensive knowledge and skills across the entire process chain,” says Martina Rauner, biotechnologist and professor at the Bone Lab Dresden. „FIDELIO is a clear commitment to Europe,” adds endocrinologist Lorenz Hofbauer. “We have top UK, Danish, Dutch, Swiss and Italian universities on board, an Austrian biotech company, and two German Universities of Excellence, TU Dresden and University of Hamburg. We expect a great conceptual and methodological exchange of young scientists at all locations. This innovation boost is good for all of us.”
The researchers and physicians involved in FIDELIO hope to use their findings to develop new prevention and treatment approaches to improve bone quality in people with type 1 and type 2 diabetes mellitus. Unravelling the diverse interactions and mechanisms of Action between glucose, fat and bone metabolism will increase our knowledge of bone health, ultimately allowing us to reduce the fracture burden and increase the quality of life of people with diabetes. In addition to gaining new scientific knowledge, the EU Marie Skłodowska-Curie programme aims to support the best scientific minds in Europe at different stages of their careers. As part of this programme, Innovative Training Networks (ITN) undertake innovative and structured training of junior researchers for up to four years, developing their potential to become leading scientists in the future.
There are 14 PhD positions open! Apply now and join us!
Congratulations to Dr. Colditz!
Another PhD from the Bone Lab: Dr. Juliane Colditz! She defended her thesis entitled “Defining the role of DKK1 in bone homeostasis and the pathogenesis of postmenopausal osteoporosis” and successfully passed the Rigorosum. At the end of the day she left with a big smile and a Summa cum laude. Well done, Juliane!
Charity run: 470 runners set signs against cancer
Charity run: 470 runners set signs against cancer
Successful start: At the first charity run of the National Center for Tumor Diseases Dresden (NCT / UCC), around 470 runners started in the Dresden Waldpark on July 2. Alone or as a team, all participants covered a distance of more than 3,100 kilometers. About 10,000 euros in donations for cancer research were made. Thanks to Martina for her active support!
Further information: https://www.nct-dresden.de/das-nctucc-dresden/spenden/benefizlauf.html
Wir waren bei der Rewe Team Challenge dabei – dem Knochen zuliebe!
Denn Laufen stärkt die Knochen
Knochen können nur stark werden und stark bleiben, wenn sie regelmäßig kräftig belastet werden. Schon dreimal 15 Laufminuten pro Woche sorgen dafür, dass das Risiko, Osteoporose zu bekommen, um bis zu 40 Prozent sinkt. Mit der Belastung steigt die Knochendichte, dies schützt vor Frakturen und Osteoporose. Knochenverlust und dessen Behandlung ist nur eines der vielen Themen, mit denen sich das Bone Lab beschäftigt.
Ulrike Baschant läuft seit vielen Jahren und trainiert regelmäßig. „Laufen gehört für mich einfach zu einem erfüllten gesunden Leben. Nach jedem Lauf fühle ich mich mental und körperlich lebendig und frisch.” Für Andy Göbel ist „Laufen eine ideale Sportart, frische Luft zu tanken und mental abzuschalten – man fühlt einfach, wie es den ganzen Körper aktiviert und Stress abbaut. Das kann nur gesund sein.” „Im Dynamo-Stadion mit tausenden anderen Sportlern ins Ziel einzulaufen, ist ein unvergleichliches Gefühl“, so Anja Strehle. Tomas Helbing, Koordinator am UniversitätsCentrum für Gesundes Altern, bereitet sich damit auf einen im Juli geplanten 24h-100km Mammut-Marsch bei München vor.
Was ist wohl für unsere vier Laufsportler das nächste Ziel? Hauptsache bewegen! Gelenke und der Stützapparat werden es danken.
Elena Tsourdi is awarded the Clinical Fellowship 2019
Elena Tsourdi is ECTS Clinical Fellowship Awardee 2019 having been granted 10.000€ for clinical research in the field of bone disease. With the project ‘The effect of antiresorptive and osteoanabolic drugs on the expression of bone-specific microRNAs in women with postmenopausal osteoporosis’ she and her collaborators plan to test whether bone-specific miRNAs are differently regulated by osteoporosis therapeutics.
MicroRNAs (miRNAs) regulate various cell functions by inhibiting target gene expression, and bone-specific miRNAs can be potential diagnostic tools in postmenopausal osteoporosis. The main goal of this project is to identify miRNAs which are involved in the pathogenesis of postmenopausal bone loss and to examine their regulation by antiresorptive and osteoanabolic drugs. We will analyse sera from an established cohort of postmenopausal women which were either treatment-naïve, or had received 1-2 yearly i.v. infusions of 5 mg zoledronic acid (ZOL), or had completed 24 months of daily s.c. injections of 20 µg teriparatide (TPTD). The central hypothesis is that bone-specific miRNAs are differently regulated by osteoporosis therapeutics. In order to test the hypothesis we will analyse miRNA-profile regulation by osteoporosis therapeutics and seek to identify correlations between miRNAs and changes in bone mineral density, serum concentrations of established bone turnover markers and myostatin in treatment-naïve and pretreated postmenopausal women. This characterization of the miRNA-profile will lead to a better understanding of the pathogenesis of postmenopausal osteoporosis and may thus contribute to the development of innovative therapeutic approaches.
Franziska Lademann wins this year’s Von Recklinghausen Prize
The German Society for Endocrinology (DGE) supports and awards outstanding achievements in basic and clinical research . The Von Recklinghausen Award honors outstanding original scientific work in the field of calcium regulating hormones and bone metabolism. Franziska Lademann won this year’s award with her work on “Lack of the thyroid hormone transporter MCT8 in osteoblast and osteoclast progenitors increases trabecular bone in male mice”! Thyroid hormones are important for maintaining a healthy bone. Their transport into target cells is mediated by transporter proteins, such as the monocarboxylate transporter 8 (Mct8). Targeted knockdown of Mct8 gene expression in bone-building osteoblasts as well as bone-degrading osteoclasts in male mice led to an increase in trabecular bone mass. Both murine models suggest that MCT8 plays an important role in bone metabolism. Further experiments are needed to reveal the exact cellular mechanisms and processes behind it. The award ceremony took place at the annual conference of the German Society of Endocrinology on 21.03.2019 in Göttingen. Congratulations!
Just in time for the “Tag der Seltenen Erkrankungen” our researchers discover protein for more mobility
Only a few know the rare bone disease FOP: as in a nightmare, muscles and connective tissue are transformed into bone – and those affected are literally walled up alive. As a result, these patients become prisoners of their own body. Scientists of the Faculty of Medicine Carl Gustav Carus at the TU Dresden have now discovered a protein that inhibits excessive bone formation in FOP. In the future, this could be a therapeutic approach. The discovery is patented and the results of the study were published in the journal “Nature Metabolism”.
A total of four million children and adults in Germany are affected by one of more than 6,000 rare diseases. Many of these diseases are still rather unexplored, and there is still no effective therapy for the majority of these diseases. Take Fibrodysplasia Ossificans Progressiva (FOP). For patients, the diagnosis means the progressive ossification of soft tissue and muscles. Healthy muscles, ligaments and tendons transform into bones – all in the wrong place – resulting in stiffness and permanent immobility as if you were permanently trapped in a cast. The growth of bone-like structures where usually no bone is (ectopic ossification) may occur without warning or is triggered by a slight bump. The underlying cause is a gene defect that leads to a defective building plan for the ACVR1 receptor.
Scientists of the Bone Lab of the University Hospital at the TU Dresden have now discovered a protein that links two apparently unrelated systems. Transferrin receptor-2 (Tfr2), responsible for iron metabolism, was discovered as a new component in bone metabolism. Tfr2 binds to so-called bone morphogenetic proteins (BMPs), which are responsible for the mineralization of bone. Together with an interdisciplinary team of international researchers, the Bone Lab has now discovered that the binding region of Tfr2 can also be used to neutralize BMPs to prevent misplaced bone formation. Professor Martina Rauner and her colleagues were surprised: “When we saw how potent the binding region of Tfr2 inhibited the undesired soft tissue ossification in the animal model, we realized that this discovery may have the potential for clinical development.” Martina Rauner, biotechnologist and scientific director of the “Bone Lab” has dedicated her career to the study of bone diseases. It took years of intensive collaboration to decipher the therapeutic potential.
So far, there is no suitable therapy for the approximately 700 patients worldwide and the 30 people affected by FOP in Germany. However, now there is new hope, states Dr Ulrike Baschant: “Kymab, a therapeutic antibody company in Cambridge, will promote the clinical development of Tfr2 based on our discovery in Dresden.” This landmark discovery is significant not only for patients with FOP, but also for those with more common skeletal disorders, such as heterotopic ossification, a disease that occurs after hip replacement surgery or major trauma. The two main authors, Martina Rauner and Ulrike Baschant, report about their finding in the journal Nature Metabolism. The discovery of the protein was the result of international cooperation for many years, amongst others with scientists from the University of Torino in Italy. With the help of a dozen scientists, they worked in the lab to solve another puzzle of science. Martina Rauner is happy that the “newly created knowledge may serve novel therapies that could improve the lives of children and adults with bone diseases”. Ulrike Baschant adds, “It is a decisive step towards regaining physical independence and personal freedom!”