Bone Tissue Engineering Lab

Headed by Eric Farrell and Andrea Lolli

Endochondral ossification for disease modelling

Research topic

Endochondral ossification is the process of developmental bone formation that occurs via a cartilage intermediate. It is an extremely complex event that involves multiple cell types, including bone cells, vessel cells and cells of the bone marrow niche. Currently it is not possible to recapitulate endochondral ossification under controlled conditions in the laboratory. This process is not only crucial for bone development and repair after injury, but it also plays a role in several debilitating diseases including osteoarthritis. As a consequence, there is a lack of in vitro models to investigate endochondral ossification in these conditions, preventing us from understanding the disease mechanisms and how to restore normal bone formation. The ability to model aspects of endochondral ossification in vitro would provide researchers with new tools to investigate the cellular and molecular basis of bone formation under physiological or pathological conditions. 

Our grup wants to develop advanced in vitro models that can reflect the complexity of vascularised bone. Taking inspiration from the natural process of endochondral ossification, we aim to generate experimental systems that accurately capture aspects of the bone formation process. Ultimately this can provide invaluable tools for fundamental research and drug screening for musculoskeletal diseases and bone-related conditions. Finally, a reliable in vitro model of bone formation will reduce or eliminate the currently unavoidable need for animals to generate bone for research purposes. 

Image: bone organoid generated by stem cells via endochondral ossification [Farrell et al., BMC Musculoskelet Disord 2011]



Andrea Lolli, Encheng Ji, Imke Janssen, Amaia Garmendia Urdalleta

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Related Publications

Calcifications in atherosclerotic plaques and impact on plaque biomechanics
Barrett, H. E., Van der Heiden, K., Farrell, E., Gijsen, F. J. H., and Akyildiz, A. C. (2019)
J Biomech 87, 1-12

Differentiation of Vascular Stem Cells Contributes to Ectopic Calcification of Atherosclerotic Plaque
Leszczynska, A., O'Doherty, A., Farrell, E., Pindjakova, J., O'Brien, F. J., O'Brien, T., Barry, F., and Murphy, M. (2016)
Stem Cells 34, 913-923

Endothelium-derived stromal cells contribute to hematopoietic bone marrow niche formation
Kenswil, K. J. G., Pisterzi, P., Sanchez-Duffhues, G., van Dijk, C., Lolli, A., Knuth, C., Vanchin, B., Jaramillo, A. C., Hoogenboezem, R. M., Sanders, M. A., Feyen, J., Cupedo, T., Costa, I. G., Li, R., Bindels, E. M. J., Lodder, K., Blom, B., Bos, P. K., Goumans, M. J., Ten Dijke, P., Farrell, E., Krenning, G., and Raaijmakers, M. (2021)
Cell Stem Cell 28, 653-670 e611

Spatiotemporal distribution of thrombospondin-4 and -5 in cartilage during endochondral bone formation and repair.

Andres Sastre, E., Maly, K., Zhu, M., Witte-Bouma, J., Trompet, D., Bohm, A. M., Brachvogel, B., van Nieuwenhoven, C. A., Maes, C., van Osch, G., Zaucke, F., and Farrell, E. (2021)
Bone 150, 115999