Hidden Secrets of the Osteohematopoietic Niche


In the osteohematopoietic niche, home of bone and blood stem cells, the aging process affects both cell types. Clinically, this translates into fragility fractures and anemia. Myelodysplastic syndrome (MDS) is a human disease of age-related impaired function of the osteohematopoietic niche. To disentangle the alterations in MDS, a comprehensive approach with suitable disease models is required.

Using big data analysis of almost 900,000 patients, we recently found that MDS patients indeed have 2-fold higher risk for osteoporosis. Moreover, treatment of cytopenia in MDS may require continuous blood transfusions posing the risk of iron overload or treatment with erythropoiesis-stimulating agents, both of which negatively impact on bone. Despite recent progress, MDS is far from being fully understood and disease-specific therapies are missing. Elucidation of key mechanisms offers the prospects of improving bone function and hematopoietic function alike. This motivated researchers at the Bone Lab to take a closer look.

Principal Investigators

Martina Rauner, PhD

Martina Rauner, PhD

«The area in which we made our first discovery that led to a patent – hopefully it will make it all the way into clinical application!»

Ulrike Baschant, PhD

Ulrike Baschant, PhD

«The area which taught me that the best scientific discoveries happen while you are busy formulating other hypotheses.»

Lorenz Hofbauer

Lorenz Hofbauer, MD

«What started as a research project on iron metabolism, turned out to be useful for treatment of major injury.»

Antonella Roetto, University of Torino, Italy
Ben Wielockx, Universitätsklinikum Dresden
Igor Theurl, Medical University Innsbruck, Austria
Yankel Gabet, Tel-Aviv University, Israel
Drorit Neumann, Tel-Aviv University, Israel
Jochen Schmitt, Center for Evidence-Based Healthcare, Universitätsklinikum Dresden
Uwe Platzbecker, Universitätsklinikum Leipzig
Martina Muckenthaler, Universitätsklinikum Heidelberg
Claudia Waskow, Fritz-Lipmann Institute, Jena
Anke Hannemann, Universität  Greifswald

Pagani A, Pettinato M, Colucci S, Dulja A, Rauner M, Nai A, Camaschella C, Altamura S, Muckenthaler MU, Silvestri L. Hemochromatosis proteins are dispensable for the acute hepcidin response to BMP2. Haematologica. 2020. (in press)

Balaian E, Weidner H, Wobus M, Baschant U, Jacobi A, Mies A, Bornhäuser M, Guck J, Hofbauer LC, Rauner M, Platzbecker U. Effects of rigosertib on the osteo-hematopoietic niche in myelodysplastic syndromes. Ann Hematol. 2019; 98:2063-2072.

Jacome-Galarza CE, Percin GI, Muller JT, Mass E, Lazarov T, Eitler J, Rauner M, Yadav VK, Crozet L, Bohm M, Loyher PL, Karsenty G, Waskow C, Geissmann F. Developmental origin, functional maintenance and genetic rescue of osteoclastsNature. 2019;568:541-545.

Rauner M, Baschant U, Roetto A, Pellegrino RM, Rother S, Salbach-Hirsch J, Weidner H, Hintze V, Campbell G, Petzold A, Lemaitre R, Henry I, Bellido T, Theurl I, Altamura S, Colucci S, Muckenthaler MU, Schett G, Komla Ebri D, Bassett JHD, Williams GR, Platzbecker U, Hofbauer LC. Transferrin receptor 2 controls bone mass and pathological bone formation via BMP and Wnt signaling. Nat Metab. 2019;1:111-124.

Balaian E, Wobus M, Weidner H, Baschant U, Stiehler M, Ehninger G, Bornhäuser M, Hofbauer LC, Rauner M, Platzbecker U. Erythropoietin inhibits osteoblast function in myelodysplastic syndromes via the canonical Wnt pathway. Haematologica. 2018;103:61-68.

Weidner H, Rauner M, Trautmann F, Schmitt J, Balaian E, Mies A, Helas S, Baschant U, Khandanpour C, Bornhäuser M, Hofbauer LC, Platzbecker U. Myelodysplastic syndromes and bone loss in mice and men. Leukemia. 2017;31:1003-1007.

Rauner M, Franke K, Murray M, Singh RP, Hiram-Bab S, Platzbecker U, Gassmann M, Socolovsky M, Neumann D, Gabet Y, Chavakis T, Hofbauer LC, Wielockx B. Increased EPO levels are associated with bone loss in mice lacking PHD2 in EPO-producing cells. J Bone Miner Res. 2016;31:1877-1887.

Baschant U, Rauner M, Balaian E, Weidner H, Roetto A, Platzbecker U, Hofbauer LC. Wnt5a is a key target for the pro-osteogenic effects of iron chelation on osteoblast progenitors. Haematologica. 2016;101:1499-1507.

Bulycheva E, Rauner M, Medyouf H, Theurl I, Bornhäuser M, Hofbauer LC, Platzbecker U. Myelodysplasia is in the niche: novel concepts and emerging therapies. Leukemia. 2015;29:259-268.